RESUMEN
Resumo Fundamento No microambiente da placa aterosclerótica, os fosfolipídios oxidados expressos na superfície de lipoproteína de baixa densidade oxidada (oxLDL) se ligam a receptores scavenger em macrófagos provocando a formação de células espumosas e a progressão da placa. Autoanticorpos contra oxLDL (oxLDL-Ab) interagem com epítopos oxidativos levando à formação de imunocomplexos que são incapazes de interagir com receptores de macrófagos, assim suprimindo a aterogênese. A liberação de oxLDL-Ab pelas células B envolve a resposta da interleucina 5 e Th2, que por sua vez são potencializadas pela HDL. Assim, levantamos a hipótese de que indivíduos com níveis mais altos de HDL-C podem apresentar níveis elevados de oxLDL-Ab. Objetivo Avaliar a relação entre os níveis de HDL-C e oxLDL-Ab. Métodos Indivíduos assintomáticos (n = 193) foram agrupados de acordo com sua concentração de HDL-C para uma das três categorias seguintes: baixa (< 68 mg/dL), intermediária (de 68 a 80 mg/dL) ou alta (> 80 mg/dL). Os valores p < 0,05 foram considerados estatisticamente significativos. Resultados Nossa análise incluiu 193 indivíduos (média etária: 47 anos; masculino: 26,3%). Em comparação com os indivíduos no menor tercil de HDL-C, os mais elevados foram mais velhos (36 versus 53 anos; p = 0,001) e, menos frequentemente, masculinos (42,6% versus 20,9%; p = 0,001). Os valores médios de oxLDL-Ab aumentaram à medida que o grupo HDL-C aumentou (0,31, 0,33 e 0,43 unidades, respectivamente; p = 0,001 para tendência). A regressão linear simples encontrou uma relação significativa e positiva entre a variável independente, HDL-C, e a variável dependente, oxLDL-Ab (R = 0,293; p = 0,009). Essa relação manteve-se significativa (R = 0,30; p = 0,044), após ajuste por covariáveis. Os níveis de apolipoproteína AI também estiveram relacionados a oxLDL-Ab nos modelos de regressão linear simples e ajustada. Conclusões HDL-C e oxLDL-Ab estão independentemente relacionados.
Abstract Background In the atherosclerotic plaque microenvironment, oxidized phospholipids expressed in the oxidized low-density lipoprotein (oxLDL) surface bind to scavenger receptors of macrophages eliciting foam cell formation and plaque progression. Auto-antibodies against oxLDL (oxLDL-Ab) interact with oxidative epitopes leading to the formation of immune complexes that are unable to interact with macrophage receptors, thus abrogating atherogenesis. Release of oxLDL-Ab by B cells involves interleukin 5 and Th2 response, which in turn are potentiated by HDL. Thereby, we hypothesized that individuals with higher levels of HDL-C may plausibly display elevated titers of oxLDL-Ab. Objective To evaluate the relationship between HDL-C and oxLDL-Ab levels. Methods Asymptomatic individuals (n = 193) were grouped according to their HDL-C concentration to one of three categories: low (< 68 mg/dL), intermediate (68 to 80 mg/dL) or high (> 80 mg/dL). P values < 0.05 were considered statistically significant. Results Our analysis included 193 individuals (mean age: 47 years; male: 26.3%). Compared to individuals in the lowest HDL-C tertile, those in the highest tertile were older (36 versus 53 years; p = 0.001) and less frequently male (42.6% versus 20.9%; p = 0.001). Mean values of oxLDL-Ab increased as the HDL-C group escalated (0.31, 0.33 and 0.43 units, respectively; p = 0.001 for trend). Simple linear regression found a significant, positive relationship between the independent variable, HDL-C, and the dependent variable, oxLDL-Ab (R = 0.293; p = 0.009). This relation remained significant (R = 0.30; p = 0.044), after adjustment by covariates. Apolipoprotein AI levels were also related to oxLDL-Ab in both simple and adjusted linear regression models. Conclusion HDL-C and oxLDL-Ab are independently related.
RESUMEN
BACKGROUND: Increased cholesterol absorption and reduced synthesis are processes that have been associated with cardiovascular disease risk in a controversial way. However, most of the studies involving markers of cholesterol synthesis and absorption include conditions, such as obesity, diabetes, dyslipidemia, which can be confounding factors. The present study aimed at investigating the relationships of plasma cholesterol synthesis and absorption markers with cardiovascular disease (CVD) risk factors, cIMT (carotid intima-media thickness), and the presence of carotid plaques in asymptomatic subjects. METHODS: A cross-sectional study was carried out in 270 asymptomatic individuals and anthropometrical parameters, fasting plasma lipids, glucometabolic profiles, high-sensitivity C-reactive protein (hs-CRP), markers of cholesterol synthesis (desmosterol and lathosterol), absorption (campesterol and sitosterol), cIMT, and the presence of atherosclerotic plaques were analyzed. RESULTS: Among the selected subjects aged between 19 and 75 years, 51% were females. Age, body mass index, systolic and diastolic blood pressure, total cholesterol, non-HDL-C, triglycerides, glucose, and lathosterol/sitosterol ratios correlated positively with cIMT (p ≤ 0.05). Atherosclerotic plaques were present in 19% of the subjects. A direct association of carotid plaques with campesterol, OR = 1.71 (95% CI = 1.04-2.82, p ≤ 0.05) and inverse associations with both ratios lathosterol/campesterol, OR = 0.29 (CI = 0.11-0.80, p ≤ 0.05) and lathosterol/sitosterol, OR = 0.45 (CI = 0.22-0.95, p ≤ 0.05) were observed in univariate logistic regression analysis. CONCLUSIONS: The findings suggested that campesterol may be associated with atherosclerotic plaques and the lathosterol/campesterol or sitosterol ratios suggested an inverse association. Furthermore, synthesis and absorption of cholesterol are inverse processes, and the absorption marker, campesterol, may reflect changes in body cholesterol homeostasis with atherogenic potential.
Asunto(s)
Enfermedades Cardiovasculares , Fitosteroles , Placa Aterosclerótica , Adulto , Anciano , Biomarcadores/metabolismo , Proteína C-Reactiva , Grosor Intima-Media Carotídeo , Colesterol/análogos & derivados , Colesterol/metabolismo , Estudios Transversales , Desmosterol , Femenino , Glucosa , Humanos , Masculino , Persona de Mediana Edad , Sitoesteroles , Triglicéridos , Adulto JovenRESUMEN
BACKGROUND: This study aimed to evaluate the associations between Lipoprotein (a) â Lp(a) levels and carotid Intima-Media Thickness (cIMT) and with carotid plaques in healthy subjects because of previous contradictory data. METHODS: A total of 317 healthy normolipidemic subjects (20â77 years old) were selected. The cIMT and atherosclerotic plaques were determined by B-mode ultrasonography. Mann-Whitney tests were performed to compare the groups according to Lp(a) levels and to explore the associations between Lp(a), carotid plaques, and cIMT, logistic and linear regression analyses were performed. RESULTS: Studied population (51% females, median age 43 years old) presented carotid plaques and cIMT ≥ 0.9 mm in 23% and 18% of the participants, respectively. The group with Lp(a) levels > 30 mg/dL presented significantly higher age and atherosclerotic plaques. Indeed, multivariate linear regression analysis showed a significant association between Lp(a), age, and race. On the other hand, logistic regression analysis demonstrated that the subjects with Lp(a) > 30 mg/dL have a significantly high risk of carotid plaques. CONCLUSION: The data from the present study indicate that Lp(a) levels above 30 mg/dL contribute to the development of carotid plaques even in apparently healthy participants.
Asunto(s)
Enfermedades de las Arterias Carótidas , Placa Aterosclerótica , Adulto , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Lipoproteína(a) , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: In the atherosclerotic plaque microenvironment, oxidized phospholipids expressed in the oxidized low-density lipoprotein (oxLDL) surface bind to scavenger receptors of macrophages eliciting foam cell formation and plaque progression. Auto-antibodies against oxLDL (oxLDL-Ab) interact with oxidative epitopes leading to the formation of immune complexes that are unable to interact with macrophage receptors, thus abrogating atherogenesis. Release of oxLDL-Ab by B cells involves interleukin 5 and Th2 response, which in turn are potentiated by HDL. Thereby, we hypothesized that individuals with higher levels of HDL-C may plausibly display elevated titers of oxLDL-Ab. OBJECTIVE: To evaluate the relationship between HDL-C and oxLDL-Ab levels. METHODS: Asymptomatic individuals (n = 193) were grouped according to their HDL-C concentration to one of three categories: low (< 68 mg/dL), intermediate (68 to 80 mg/dL) or high (> 80 mg/dL). P values < 0.05 were considered statistically significant. RESULTS: Our analysis included 193 individuals (mean age: 47 years; male: 26.3%). Compared to individuals in the lowest HDL-C tertile, those in the highest tertile were older (36 versus 53 years; p = 0.001) and less frequently male (42.6% versus 20.9%; p = 0.001). Mean values of oxLDL-Ab increased as the HDL-C group escalated (0.31, 0.33 and 0.43 units, respectively; p = 0.001 for trend). Simple linear regression found a significant, positive relationship between the independent variable, HDL-C, and the dependent variable, oxLDL-Ab (R = 0.293; p = 0.009). This relation remained significant (R = 0.30; p = 0.044), after adjustment by covariates. Apolipoprotein AI levels were also related to oxLDL-Ab in both simple and adjusted linear regression models. CONCLUSION: HDL-C and oxLDL-Ab are independently related.
FUNDAMENTO: No microambiente da placa aterosclerótica, os fosfolipídios oxidados expressos na superfície de lipoproteína de baixa densidade oxidada (oxLDL) se ligam a receptores scavenger em macrófagos provocando a formação de células espumosas e a progressão da placa. Autoanticorpos contra oxLDL (oxLDL-Ab) interagem com epítopos oxidativos levando à formação de imunocomplexos que são incapazes de interagir com receptores de macrófagos, assim suprimindo a aterogênese. A liberação de oxLDL-Ab pelas células B envolve a resposta da interleucina 5 e Th2, que por sua vez são potencializadas pela HDL. Assim, levantamos a hipótese de que indivíduos com níveis mais altos de HDL-C podem apresentar níveis elevados de oxLDL-Ab. OBJETIVO: Avaliar a relação entre os níveis de HDL-C e oxLDL-Ab. MÉTODOS: Indivíduos assintomáticos (n = 193) foram agrupados de acordo com sua concentração de HDL-C para uma das três categorias seguintes: baixa (< 68 mg/dL), intermediária (de 68 a 80 mg/dL) ou alta (> 80 mg/dL). Os valores p < 0,05 foram considerados estatisticamente significativos. RESULTADOS: Nossa análise incluiu 193 indivíduos (média etária: 47 anos; masculino: 26,3%). Em comparação com os indivíduos no menor tercil de HDL-C, os mais elevados foram mais velhos (36 versus 53 anos; p = 0,001) e, menos frequentemente, masculinos (42,6% versus 20,9%; p = 0,001). Os valores médios de oxLDL-Ab aumentaram à medida que o grupo HDL-C aumentou (0,31, 0,33 e 0,43 unidades, respectivamente; p = 0,001 para tendência). A regressão linear simples encontrou uma relação significativa e positiva entre a variável independente, HDL-C, e a variável dependente, oxLDL-Ab (R = 0,293; p = 0,009). Essa relação manteve-se significativa (R = 0,30; p = 0,044), após ajuste por covariáveis. Os níveis de apolipoproteína AI também estiveram relacionados a oxLDL-Ab nos modelos de regressão linear simples e ajustada. CONCLUSÕES: HDL-C e oxLDL-Ab estão independentemente relacionados.
RESUMEN
Non-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity.
RESUMEN
Several proteins are involved in cholesterol homeostasis, as scavenger receptor class B type I and ATP-binding cassette (ABC) transporters including ABCA1, ABCG1, ABCG5, and ABCG8. This study aimed to determine the effects of single nucleotide variants (SNVs) rs2275543 (ABCA1), rs1893590 (ABCG1), rs6720173 (ABCG5), rs6544718 (ABCG8), and rs5888 (SCARB1) on plasma lipids, lipoproteins, and adiposity markers in an asymptomatic population and its sex-specific effects. Volunteers (n = 590) were selected and plasma lipids, lipoproteins, and adiposity markers (waist-to-hip and waist-to-height ratios, lipid accumulation product and body adiposity index) were measured. Genomic DNA was isolated from peripheral blood cells according to the method adapted from Gross-Bellard. SNVs were detected in the TaqMan® OpenArray® Real-Time polymerase chain reaction platform and data analyses were performed using the TaqMan® Genotyper Software. The rs2275543*C point to an increase of high-density lipoprotein size in females while in males very-low-density lipoprotein, cholesterol, and triglycerides were statistically lower (P value < 0.05). The rs1893590*C was statistically associated with lower apolipoprotein A-I levels and higher activities of paraoxonase-1 and cholesteryl ester transfer protein (P value < 0.05). The rs6720173 was statistically associated with an increase in cholesterol and low-density lipoprotein cholesterol in males; moreover, rs6544718*T reduced adiposity markers in females (P value < 0.05). Regarding the rs5888, a decreased adiposity marker in the total population and in females occurred (P value < 0.05). Multivariate analysis of variance showed that SNVs could influence components of high-density lipoprotein metabolism, mainly through ABCG1 (P value < 0.05). The ABCA1 and ABCG5 variants showed sex-specific effects on lipids and lipoproteins, while SCARB1 and ABCG8 variants might influence adiposity markers in females. Our data indicate a possible role of ABCG1 on HDL metabolism.
Asunto(s)
Adiposidad , Lipoproteínas , Transportador 1 de Casete de Unión a ATP/genética , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/metabolismo , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8/genética , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Adiposidad/genética , Colesterol/metabolismo , Femenino , Humanos , Lipoproteínas/genética , Lipoproteínas/metabolismo , Lipoproteínas HDL/genética , Masculino , Receptores Depuradores de Clase B/genética , Receptores Depuradores de Clase B/metabolismoRESUMEN
Abstract Background: This study aimed to evaluate the associations between Lipoprotein (a) ‒ Lp(a) levels and carotid Intima-Media Thickness (cIMT) and with carotid plaques in healthy subjects because of previous contradictory data. Methods: A total of 317 healthy normolipidemic subjects (20‒77 years old) were selected. The cIMT and atherosclerotic plaques were determined by B-mode ultrasonography. Mann-Whitney tests were performed to compare the groups according to Lp(a) levels and to explore the associations between Lp(a), carotid plaques, and cIMT, logistic and linear regression analyses were performed. Results: Studied population (51% females, median age 43 years old) presented carotid plaques and cIMT ≥ 0.9 mm in 23% and 18% of the participants, respectively. The group with Lp(a) levels > 30 mg/dL presented significantly higher age and atherosclerotic plaques. Indeed, multivariate linear regression analysis showed a significant association between Lp(a), age, and race. On the other hand, logistic regression analysis demonstrated that the subjects with Lp(a) > 30 mg/dL have a significantly high risk of carotid plaques. Conclusion: The data from the present study indicate that Lp(a) levels above 30 mg/dL contribute to the development of carotid plaques even in apparently healthy participants.
RESUMEN
The common genetic variant in the promoter region of the hepatic lipase gene [LIPC -250G/A(rs2070895)] has an ambiguous association with cardiovascular disease. In this context, our study was performed to identify the relationships between the rs2070895 with carotid atherosclerosis, plasma lipids, and parameters of reverse cholesterol transport. A total of 285 normolipidemic and asymptomatic participants from an initial sample of 598,288 individuals (inclusion criteria: LDL-C ≤130 mg/dL and triglycerides ≤150 mg/dL; age: 20-75 years, both genders; confirmation of clinical, anthropometric and laboratory data; attended all visits; DNA was achieved to perform genetic analysis) were enrolled and the rs2070895 variant was genotyped by TaqMan® OpenArray® Plataform. Carotid intima-media thickness and the screening of atherosclerotic plaques were determined by B-mode ultrasonography. The rs2070895 genotype frequencies were 0.44, 0.41, and 0.15 (GG, GA, and AA, respectively). Logistic regression analysis showed that the risk of having plaques was increased in participants carrying the AA or AG genotypes (OR = 3.90; 95% CI = 1.54-10.33), despite an increase in high-density lipoprotein cholesterol levels, HDL diameter and apolipoprotein A-I, as compared to the GG genotype. Hepatic lipase and endogenous lecithin cholesterol acyl transferase activities were reduced (38% and 19%, respectively) and lipoprotein lipase was increased by 30% (AA vs GG). Our results provide evidence that the AA or AG genotypes of the rs2070895 were associated with carotid atherosclerosis in apparently healthy participants, probably as a consequence of reduced reverse cholesterol transport and accumulation of HDL subfraction 2 rich in triglycerides and depleted in cholesteryl esters that could become dysfunctional.
Asunto(s)
Enfermedades de las Arterias Carótidas/genética , Lipasa/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Enfermedades Asintomáticas , Brasil , Enfermedades de las Arterias Carótidas/sangre , Colesterol/sangre , Femenino , Estudios de Asociación Genética , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Abstract Background: Among dyslipidemias, hypercholesterolemia is considered the main risk factor for cardiovascular diseases in adults. In childhood and adolescence, elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are positively associated with atherosclerosis markers, however, systematic screening for dyslipidemias in these groups is a controversial topic. Objective: To characterize the frequencies, types and severity of dyslipidemias in children and adolescents attended at the Basic Health Units managed by SUS in Campinas/SP. Methods: After an agreement with the Municipal Health Department of Campinas, consecutive results of serum lipid profiles (n = 312,650) of individuals of both sexes (n = 62,530) aged between 1 day old and 19 years were obtained, from 2008 to 2015. Age groups and dyslipidemias were classified according to recommendations in the literature. The statistical significance level adopted was the probability value (p) of 0.05 or less. Results: The observed frequencies of increased TC, triglycerides (TG), LDL-C and non-HDL-C (NHDL-C) were 33%, 40%, 29% and 13% respectively, and of reduced high-density lipoprotein cholesterol (HDL-C) the frequency was 39%. The frequencies, in general, were greater in females and in the southwest and south regions of the city, whose populations are more vulnerable from the socioeconomic point of view; on the other hand, in children and adolescents, the frequencies of TG and HDL-C prevailed, respectively. Conclusions: The high frequency and regionalization of dyslipidemias in children and adolescents indicate the need for specific actions in the handling and treatment of such diseases by the public health system of Campinas.
Resumo Fundamento: Dentre as dislipidemias, a hipercolesterolemia é considerada o principal fator de risco para doenças cardiovasculares em adultos. Na infância e adolescência, a elevação de colesterol total (CT) e colesterol da lipoproteína de baixa densidade (LDL-C) associam-se positivamente a marcadores de aterosclerose, entretanto, a triagem sistemática para dislipidemias nestes grupos é um tema controverso. Objetivos: Caracterizar as frequências, tipos e gravidade de dislipidemias em crianças e adolescentes atendidos nas Unidades Básicas de Saúde (UBS) mantidas pelo SUS em Campinas/SP. Métodos: A partir do convênio com a Secretaria Municipal de Saúde de Campinas foram obtidos resultados consecutivos de perfis lipídicos séricos (n = 312.650) de indivíduos de ambos os sexos (n = 62.530), com idade entre 1 dia e 19 anos, entre 2008 e 2015. Grupos etários e dislipidemias foram classificados conforme recomendações da literatura. O nível de significância estatístico considerado significativo foi de p < 0,05. Resultados: As frequências observadas de CT, triglicérides (TG), LDL-C e não HDL-C (NHDL-C) aumentados foram, respectivamente 33%, 40%, 29% e 13% e de redução do colesterol da lipoproteína de alta densidade (HDL-C) 39%, no total, sendo maiores no sexo feminino e nas regiões sudoeste e sul da cidade, mais vulneráveis do ponto de vista socioeconômico; já em infantes a de TG, e nos adolescentes a de HDL-C prevaleceram. Conclusões: A alta frequência e a regionalização das dislipidemias em crianças e adolescentes apontam para a necessidade de ações específicas no manuseio e tratamento destas no âmbito do sistema público de saúde em Campinas.
Asunto(s)
Humanos , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Lípidos/sangre , Índice de Severidad de la Enfermedad , Brasil/epidemiología , Estudios Transversales , Estudios Retrospectivos , Factores de Riesgo , Distribución por Edad , Dislipidemias/diagnóstico , Dislipidemias/sangre , Mapeo GeográficoRESUMEN
BACKGROUND: Among dyslipidemias, hypercholesterolemia is considered the main risk factor for cardiovascular diseases in adults. In childhood and adolescence, elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are positively associated with atherosclerosis markers, however, systematic screening for dyslipidemias in these groups is a controversial topic. OBJECTIVE: To characterize the frequencies, types and severity of dyslipidemias in children and adolescents attended at the Basic Health Units managed by SUS in Campinas/SP. METHODS: After an agreement with the Municipal Health Department of Campinas, consecutive results of serum lipid profiles (n = 312,650) of individuals of both sexes (n = 62,530) aged between 1 day old and 19 years were obtained, from 2008 to 2015. Age groups and dyslipidemias were classified according to recommendations in the literature. The statistical significance level adopted was the probability value (p) of 0.05 or less. RESULTS: The observed frequencies of increased TC, triglycerides (TG), LDL-C and non-HDL-C (NHDL-C) were 33%, 40%, 29% and 13% respectively, and of reduced high-density lipoprotein cholesterol (HDL-C) the frequency was 39%. The frequencies, in general, were greater in females and in the southwest and south regions of the city, whose populations are more vulnerable from the socioeconomic point of view; on the other hand, in children and adolescents, the frequencies of TG and HDL-C prevailed, respectively. CONCLUSIONS: The high frequency and regionalization of dyslipidemias in children and adolescents indicate the need for specific actions in the handling and treatment of such diseases by the public health system of Campinas.
Asunto(s)
Dislipidemias/epidemiología , Lípidos/sangre , Adolescente , Distribución por Edad , Brasil/epidemiología , Niño , Preescolar , Estudios Transversales , Dislipidemias/sangre , Dislipidemias/diagnóstico , Mapeo Geográfico , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL). To investigate the relationships between p.Q192R SNP of We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317). The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques. In low-risk individuals, the presence of the p.192Q variant of
Evidências sugerem que a paroxonase 1 (PON1) confere importantes propriedades antioxidantes e antiinflamatórias quando associada à lipoproteína de alta densidade (HDL). Investigar as relações entre o SNP p.Q192R da Foram estudados 584 voluntários (mulheres, n = 326; homens, n = 258; idade entre 19-75 anos). Foi extraído DNA genômico total e o SNP foi detectado na plataforma de genotipagem TaqMan® SNP OpenArray® (Applied Biosystems, Foster City, CA). Foram dosadas lipoproteínas e apolipoproteínas plasmáticas, e a atividade da PON1 foi medida utilizando-se paraoxon como substrato. Foi utilizada ultrassonografia bidimensional de alta resolução para determinar a espessura íntimo‑medial das artérias carótidas (EIMc) e a presença de placas ateroscleróticas carotídeas em um subgrupo de indivíduos (n = 317). A presença de p.192Q esteve associada a um aumento significativo da atividade da PON1 (RR = 12,30 (11,38); RQ = 46,96 (22,35); QQ = 85,35 (24.83) μmol/min; p < 0,0001), HDL-C (RR = 45 (37); RQ = 62 (39); QQ= 69 (29) mg/dL; p < 0,001) e apo A-1 (RR = 140,76 ± 36,39; RQ = 147,62 ± 36,92; QQ = 147,49 ± 36,65 mg/dL; p = 0,019). A análise de regressão Asunto(s)
Adulto
, Anciano
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Adulto Joven
, Arildialquilfosfatasa/genética
, Enfermedades de las Arterias Carótidas/genética
, Lipoproteínas/genética
, Polimorfismo de Nucleótido Simple
, Arildialquilfosfatasa/sangre
, Brasil
, Grosor Intima-Media Carotídeo
, Enfermedades de las Arterias Carótidas/etnología
, Enfermedades de las Arterias Carótidas
, Estudios de Asociación Genética
, Lipoproteínas/sangre
, Reacción en Cadena en Tiempo Real de la Polimerasa
, Valores de Referencia
, Análisis de Regresión
, Factores de Riesgo
RESUMEN
BACKGROUND: Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL). OBJECTIVE: To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample. METHODS: We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution ß-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317). RESULTS: The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) µmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques. CONCLUSION: In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.
Asunto(s)
Arildialquilfosfatasa/genética , Enfermedades de las Arterias Carótidas/genética , Lipoproteínas/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Arildialquilfosfatasa/sangre , Brasil , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/etnología , Grosor Intima-Media Carotídeo , Femenino , Estudios de Asociación Genética , Humanos , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Valores de Referencia , Análisis de Regresión , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Misclassification of patients as low cardiovascular risk (LCR) remains a major concern and challenges the efficacy of traditional risk markers. Due to its strong association with cholesterol acceptor capacity, high-density lipoprotein (HDL) size has been appointed as a potential risk marker. Hence, we investigate whether HDL size improves the predictive value of HDL-cholesterol in the identification of carotid atherosclerotic burden in individuals stratified to be at LCR. METHODS AND FINDINGS: 284 individuals (40-75 years) classified as LCR by the current US guidelines were selected in a three-step procedure from primary care centers of the cities of Campinas and Americana, SP, Brazil. Apolipoprotein B-containing lipoproteins were precipitated by polyethylene glycol and HDL size was measured by dynamic light scattering (DLS) technique. Participants were classified in tertiles of HDL size (<7.57; 7.57-8.22; >8.22 nm). Carotid intima-media thickness (cIMT) <0.90 mm (80th percentile) was determined by high resolution ultrasonography and multivariate ordinal regression models were used to assess the association between cIMT across HDL size and levels of lipid parameters. HDL-cholesterol was not associated with cIMT. In contrast, HDL size >8.22 nm was independently associated with low cIMT in either unadjusted and adjusted models for age, gender and Homeostasis Model Assessment 2 index for insulin sensitivity, ethnicity and body mass index (Odds ratio 0.23; 95% confidence interval 0.07-0.74, pâ=â0.013). CONCLUSION: The mean HDL size estimated with DLS constitutes a better predictor for subclinical carotid atherosclerosis than the conventional measurements of plasma HDL-cholesterol in individuals classified as LCR.
Asunto(s)
Aterosclerosis/sangre , Enfermedades de las Arterias Carótidas/sangre , HDL-Colesterol/sangre , Adulto , Anciano , Enfermedades Asintomáticas , Aterosclerosis/diagnóstico , Enfermedades de las Arterias Carótidas/diagnóstico , HDL-Colesterol/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Medición de Riesgo , Factores de RiesgoRESUMEN
The secondhand exposure to cigarette smoke is being considered evil, and damage caused by this passive exposure has been proven by several studies. To investigate the effects of sidestream smoke exposure on random-pattern skin flap survival, 20 female rats were separated into 2 groups: group A (n = 10) was exposed 6 weeks to the smoke from the burning cigarette (passive smoking) and group B (n = 10) was the control group. After 6 weeks of exposition, a dorsal McFarlane flap of 4 × 10 cm was performed in all rats. Two weeks after this procedure, the ratio of necrotic and total areas was calculated using computer programs. The median area of necrosis in group A was 29.5%, significantly higher than that in group B with 17.5% (P < 0.024). In conclusion, this study suggests increased risk of random-pattern skin flap necrosis after sidestream exposure to cigarette smoke.
Asunto(s)
Supervivencia de Injerto , Complicaciones Posoperatorias/etiología , Colgajos Quirúrgicos/patología , Contaminación por Humo de Tabaco/efectos adversos , Animales , Femenino , Necrosis/etiología , Distribución Aleatoria , Ratas , Ratas Wistar , Factores de RiesgoRESUMEN
BACKGROUND: We have searched if plasma high density lipoprotein-cholesterol (HDL-C) concentration interferes simultaneously with whole-body cholesterol metabolism and insulin sensitivity in normal weight healthy adult subjects. METHODS: We have measured the activities of several plasma components that are critically influenced by insulin and that control lipoprotein metabolism in subjects with low and high HDL-C concentrations. These parameters included cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), lecithin cholesterol acyl transferase (LCAT), post-heparin lipoprotein lipase (LPL), hepatic lipase (HL), pre-beta-1HDL, and plasma sterol markers of cholesterol synthesis and intestinal absorption. RESULTS: In the high-HDL-C group, we found lower plasma concentrations of triglycerides, alanine aminotransferase, insulin, HOMA-IR index, activities of LCAT and HL compared with the low HDL-C group; additionally, we found higher activity of LPL and pre-beta-1HDL concentration in the high-HDL-C group. There were no differences in the plasma CETP and PLTP activities. CONCLUSIONS: These findings indicate that in healthy hyperalphalipoproteinemia subjects, several parameters that control the metabolism of plasma cholesterol and lipoproteins are related to a higher degree of insulin sensitivity.
Asunto(s)
HDL-Colesterol/sangre , Resistencia a la Insulina , Insulina/sangre , Adulto , Anciano , Biomarcadores/sangre , Brasil , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Proteínas de Transferencia de Ésteres de Colesterol/deficiencia , VLDL-Colesterol/sangre , Femenino , Voluntarios Sanos , Humanos , Peso Corporal Ideal , Absorción Intestinal , Lipasa/sangre , Metabolismo de los Lípidos , Errores Innatos del Metabolismo Lipídico/sangre , Lipoproteína Lipasa/sangre , Masculino , Persona de Mediana Edad , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Proteínas de Transferencia de Fosfolípidos/sangre , Adulto JovenRESUMEN
Assessment of lipid profile parameters has been considered a cornerstone in classifying individuals and populations at risk for cardiovascular disease. Recently, however, preliminary data have raised the possibility of seasonal variations in these parameters, which may cause under- or overestimation. Biological rhythms and seasonal variation of lipid profile was investigated in 227 359 consecutive individuals who underwent health checkups in primary care centers between 2008 and 2010. Plasma low-density lipoprotein cholesterol (LDL-C) >130 mg/dL was 8% more prevalent during winter than summer, with a larger difference among women and middle-aged adults (p < 0.001). High-density lipoprotein cholesterol (HDL-C) <40 mg/dL and triglycerides (TG) >150 mg/dL were respectively 9% and 5% more prevalent during the summer (p < 0.001). Variation amplitude was 3.4 ± 0.3 mg/dL for HDL-C (p = 0.005), 7 ± 2 mg/dL for LDL-C (p = 0.047), and 12 ± 9 mg/dL for TG (p = 0.058). Based on a large population sample, this study confirms the existence of biological rhythms and seasonal variation in lipid profile. This finding must be particularly accounted for in cross-sectional analyses of relative risk, prevalence, or the rate of goal achievement for lipid parameters.
Asunto(s)
Dislipidemias/epidemiología , Periodicidad , Estaciones del Año , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Brasil/epidemiología , Niño , Preescolar , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Dislipidemias/sangre , Dislipidemias/diagnóstico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Dinámicas no Lineales , Prevalencia , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Factores de Tiempo , Triglicéridos/sangre , Adulto JovenRESUMEN
INTRODUCTION: The development of research for diagnosis, prevention and treatment of atherosclerotic cardiovascular disease is of utmost importance due to the fact that it is the main cause of morbidity and mortality in Brazil. OBJECTIVE: To demonstrate the phases of the selection process for candidates with the aim to develop a clinical-laboratorial database of hyper alpha lipoproteinemic patients (hyper A) - high density lipoprotein cholesterol (HDL-C) ≥ 68 mg/dl) and hypo alpha lipoproteinemic patients (hypo A) - HDL-C < 39 mg/dl. MATERIAL AND METHODS: The volunteers were contacted after selection of lipid profiles from individuals treated at the Sistema Único de Saúde (SUS), Campinas-SP and neighboring area. Afterwards, the selected patients went through blood collection, clinical examinations and answered questionnaires on dietary frequency and physical activity. After this preliminary evaluation, some individuals were convened to another blood collection and, subsequently, were submitted to an ultrasonographic exam of the carotid arteries. RESULTS: Only 0.6% and 0.3% from 598,288 lipid profiles were selected for hyper A and hypo A groups, respectively, including gender disparity. Lack of effective questionnaires (75%), missing calls (60%) and non-inclusion were the major hindrances in the construction of this database. DISCUSSION: The difficulties to obtain eligible candidates were also due to the low prevalence of both groups hypo A and hyper A and the high prevalence of pathologies that contribute to non-genetic variations of HDL-C. CONCLUSION: In spite of the obstacles in the development of this database, this study brought about several scientific publications. Furthermore, the development of molecular analyzes and functionality will shortly generate other findings, contributing to the diagnosis and follow-up of HDL dyslipidemias.
INTRODUÇÃO: O desenvolvimento de pesquisa para diagnóstico e prevenção da doença aterosclerótica cardiovascular no Brasil é de grande importância por esta ser a principal causa de morbimortalidade no país. OBJETIVO: Demonstrar as etapas do processo de seleção de voluntários para a construção de um banco de dados clínico-laboratorial de indivíduos hiperalfalipoproteinêmicos (hiper A) - colesterol da lipoproteína de alta densidade (HDL-C) ≥ 68 mg/dl - e hipoalfalipoproteinêmicos (hipo A) - HDL-C < 39 mg/dl. MATERIAL E MÉTODOS: Os voluntários são contatados a partir de resultados de perfis lipídicos de indivíduos atendidos pelo Sistema Único de Saúde (SUS) de Campinas-SP e região e, se selecionados, são convidados para coleta de sangue, exames clínicos e responder a questionários de atividade física e de frequência alimentar. Após essa avaliação, os indivíduos podem ser convocados para nova coleta de sangue e, posteriormente, para a ultrassonografia de carótidas. RESULTADOS: Entre 598.288 perfis lipídicos recebidos das redes públicas, apenas 0,6% e 0,3% compuseram os nossos grupos hiper A e hipo A, com disparidade entre os gêneros. A falta de questionários efetivos (75%), das chamadas não atendidas (60%) e a não inclusão foram os pontos mais difíceis na construção do banco de dados. DISCUSSÃO: A dificuldade de obtenção de voluntários elegíveis também se deve à baixa prevalência de hipo A e hiper A e à alta prevalência de patologias que contribuem para variações não genéticas do HDL-C. CONCLUSÃO: Apesar das dificuldades na criação da base de dados, este estudo gerou várias publicações e, com o desenvolvimento das análises moleculares e da funcionalidade, muitas outras seguirão em curto período, fatos contribuintes para o diagnóstico e o acompanhamento das dislipidemias envolvendo a HDL.
RESUMEN
FUNDAMENTO: A atividade do óxido nítrico sintase endotelial (eNOS) pode ser modulada pelo colesterol da lipoproteína de alta densidade (HDL-C), estatinas ou polimorfismos, como o T-786C de eNOS. OBJETIVO: Este estudo teve como objetivo avaliar se o polimorfismo T-786C está associado a alterações nos efeitos da atorvastatina no perfil lipídico, nas concentrações de metabólitos de óxido nítrico (NO) e da proteína C reativa de alta sensibilidade (PCR-as). MÉTODOS: Trinta voluntários do sexo masculino, assintomáticos, com idade entre 18-56 anos foram genotipados e classificados de acordo com a ausência (TT, n = 15) ou presença (CC, n = 15) do polimorfismo. Eles foram selecionados aleatoriamente para a utilização de placebo e atorvastatina (10 mg/dia por 14 dias). Após cada tratamento foram medidos lípides, lipoproteínas, frações HDL2 e HDL3, atividade da proteína de transferência de colesteril éster (CETP), metabólitos de NO e PCR-as. RESULTADOS: As comparações entre genótipos após a administração de placebo mostraram aumento da atividade da CETP polimorfismo-dependente (TT, 12 ± 7; CC, 22 ± 12, p < 0,05). As análises da interação entre os tratamentos indicaram que a atorvastatina tem efeito sobre colesterol, LDL, nitrito e razões lípides/proteínas (HDL2 e HDL3) (p < 0,001) em ambos os genótipos. É interessante notar as interações genótipo/droga sobre a CETP (p < 0,07) e a lipoproteína (a) [Lp(a)] (p < 0,056), levando a uma diminuição limítrofe da CETP, embora sem afetar a Lp(a). A PRC-as não mostrou alterações. CONCLUSÃO: Os resultados sugerem que o tratamento com estatinas pode ser relevante para a prevenção primária da aterosclerose em pacientes com o polimorfismo T-786C do eNOS, considerando os efeitos no metabolismo lipídico.
BACKGROUND: Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS. OBJECTIVE: This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP). METHODS: Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated. RESULTS: The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12±7; CC, 22±12; p < 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p < 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p < 0.07) and lipoprotein (a) (Lp(a)) (p < 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration. CONCLUSION: These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism.
Asunto(s)
Adolescente , Adulto , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Ácidos Heptanoicos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo Genético/genética , Pirroles/farmacología , Análisis de Varianza , Proteína C-Reactiva/análisis , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Ácidos Heptanoicos/sangre , Óxido Nítrico Sintasa de Tipo III/sangre , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Óxido Nítrico/sangre , Pirroles/sangre , Método Simple Ciego , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
BACKGROUND: Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS. OBJECTIVE: This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP). METHODS: Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated. RESULTS: The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12±7; CC, 22±12; p < 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p < 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p < 0.07) and lipoprotein (a) (Lp(a)) (p < 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration. CONCLUSION: These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism.
Asunto(s)
Ácidos Heptanoicos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo Genético/genética , Pirroles/farmacología , Adolescente , Adulto , Análisis de Varianza , Atorvastatina , Proteína C-Reactiva/análisis , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Ácidos Heptanoicos/sangre , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/sangre , Óxido Nítrico Sintasa de Tipo III/sangre , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Pirroles/sangre , Método Simple Ciego , Estadísticas no Paramétricas , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Cholesteryl ester transfer protein (CETP) plays a major role in lipid metabolism, but studies on the association of CETP polymorphisms with risks of cardiovascular disease are inconsistent. This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample. METHODS: The polymorphisms were analyzed using polymerase chain reaction in 207 adult volunteers. Serum lipid profiles, oxLDL Ab titers, C-reactive protein and tumor necrosis factor-α concentrations and CETP and phospholipid transfer protein (PLTP) activities were determined, and common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. RESULTS: No differences in cIMT were observed between the presence or absence of the minor B2 and V alleles in either polymorphism. However, inverse correlations between mean cIMT and CETP activity in the presence of these polymorphisms were observed, and positive correlations of these polymorphisms with PLTP activity and oxLDL Ab titers were identified. Moreover, logistic multivariate analysis revealed that the presence of the B2 allele was associated with a 5.1-fold (CI 95%, OR: 1.26 - 21.06) increased risk for cIMT, which was equal and above the 66th percentile and positively interacted with age. However, no associations with the V allele or CETP and PLTP activities were observed. CONCLUSIONS: None of the studied parameters, including CETP activity, explained the different relationships between these polymorphisms and cIMT, suggesting that other non-determined factors were affected by the genotypes and related to carotid atherosclerotic disease.