RESUMEN
The hepatic lipase (LIPC) locus is a well-established determinant of high-density lipoprotein cholesterol (HDL-C) concentrations, an association that is modified by dietary fat in observational studies. Dietary interventions are lacking. We investigated dietary modulation of LIPC rs1800588 (-514 C/T) for lipids and glucose using a randomized crossover design comparing a high-fat Western diet and a low-fat traditional Hispanic diet in individuals of Caribbean Hispanic descent (n = 42, 4 wk/phase). No significant gene-diet interactions were observed for HDL-C. However, differences in dietary response according to LIPC genotype were observed. In major allele carriers (CC/CT), HDL-C (mmol/l) was higher following the Western diet compared with the Hispanic diet: phase 1 (Western: 1.3 ± 0.03; Hispanic: 1.1 ± 0.04; P = 0.0004); phase 2 (Western: 1.4 ± 0.03; Hispanic: 1.2 ± 0.03; P = 0.0003). In contrast, HDL-C in TT individuals did not differ by diet. Only major allele carriers benefited from the higher-fat diet for HDL-C. Secondarily, we explored dietary fat quality and rs1800588 for HDL-C and triglycerides (TG) in a Boston Puerto Rican Health Study (BPRHS) subset matched for diabetes and obesity status (subset n = 384). In the BPRHS, saturated fat was unfavorably associated with HDL-C and TG in rs1800588 TT carriers. LIPC rs1800588 appears to modify plasma lipids in the context of dietary fat. This new evidence of genetic modulation of dietary responses may inform optimal and personalized dietary fat advice and reinforces the importance of studying genetic markers in diet and cardiometabolic health.
Asunto(s)
HDL-Colesterol/sangre , Grasas de la Dieta/farmacología , Lipasa/genética , Adulto , HDL-Colesterol/genética , Estudios Transversales , Dieta Alta en Grasa/efectos adversos , Femenino , Prueba de Tolerancia a la Glucosa , Hispánicos o Latinos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Puerto RicoRESUMEN
Genetic variation in fatty acid desaturases (FADS) has previously been linked to long-chain polyunsaturated fatty acids (PUFAs) in adipose tissue and cardiovascular risk. The goal of our study was to test associations between six common FADS polymorphisms (rs174556, rs3834458, rs174570, rs2524299, rs174589, rs174627), intermediate cardiovascular risk factors, and non-fatal myocardial infarction (MI) in a matched population based case-control study of Costa Rican adults (n = 1756). Generalized linear models and multiple conditional logistic regression models were used to assess the associations of interest. Analyses involving intermediate cardiovascular risk factors and MI were also conducted in two replication cohorts, The Nurses' Health Study (n = 1200) and The Health Professionals Follow-Up Study (n = 1295). In the Costa Rica Study, genetic variation in the FADS cluster was associated with a robust linear decrease in adipose gamma-linolenic, arachidonic, and eicosapentaenoic fatty acids, and significant or borderline significant increases in the eicosadienoic, eicosatrienoic, and dihomo-gamma-linolenic fatty acids. However, the associations with adipose tissue fatty acids did not translate into changes in inflammatory biomarkers, blood lipids, or the risk of MI in the discovery or the replication cohorts. In conclusion, fatty acid desaturase polymorphisms impact long-chain PUFA biosynthesis, but their overall effect on cardiovascular health likely involves multiple pathways and merits further investigation.
RESUMEN
BACKGROUND/OBJECTIVES: Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population. SUBJECTS/METHODS: MI cases (n=1650) were matched to population-based controls (n=1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses' Health Study (n=1200) and The Health Professionals Follow-Up Study (n=1295). RESULTS: Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values=0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value=0.04). However, the observed associations were not replicated in independent populations. CONCLUSION: Common genetic variants in elongases are not associated with adipose tissue fatty acids, serum lipids, biomarkers of systemic inflammation, or the risk of MI.
Asunto(s)
Acetiltransferasas/genética , Enfermedades Cardiovasculares/genética , Colesterol/genética , Ácidos Grasos Insaturados/genética , Inflamación/genética , Infarto del Miocardio/genética , Polimorfismo Genético , Tejido Adiposo/metabolismo , Anciano , Alelos , Estudios de Casos y Controles , Colesterol/sangre , LDL-Colesterol/sangre , LDL-Colesterol/genética , Costa Rica , Elongasas de Ácidos Grasos , Ácidos Grasos Insaturados/biosíntesis , Femenino , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fenotipo , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: The APOA1/C3/A4/A5 cluster encodes key regulators of plasma lipids. Interactions between dietary factors and single nucleotide polymorphisms (SNPs) in the cluster have been reported. Allostatic load, or physiological dysregulation in response to stress, has been implicated in shaping health disparities in ethnic groups. We aimed to determine the association between polymorphisms in the APOA1/C3/A4/A5 cluster with allostatic load parameters, alone, and in interaction with dietary fat intake in Puerto Ricans adults. METHODS AND RESULTS: Data on demographic and anthropometric measures, lifestyle behaviors, and medication use, as well as blood and urine samples for biomarker analysis, were obtained from participants of the Boston Puerto Rican Health Study (n=821, age 45-75 y). The 12 polymorphisms analyzed were not associated with allostatic load parameters. Significant interactions were observed between dietary fat intake and APOA1-75 in association with waist circumference (WC), (P=0.005), APOC3-640 with diastolic blood pressure (DBP), (P=0.003), and APOA4 N147S and APOA5 S19W with systolic blood pressure (SBP), (P=0.001 and P=0.002, respectively). Puerto Ricans homozygous for the common allele of APOA1-75, APOA4 N147S and APOA5 S19W had lower WC and SBP when consuming <31% of total fat from energy, than participants with the minor allele. Participants heterozygous for APOC3-640 had lower DBP at total fat intake ≥31% from energy. CONCLUSION: SNPs in APOA1/C3/A4/A5, as modulated by dietary fat intake, appear to influence allostatic load parameters in Puerto Ricans.
Asunto(s)
Alostasis/genética , Apolipoproteína A-I/genética , Apolipoproteína C-III/genética , Apolipoproteínas A/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Apolipoproteína A-V , Presión Sanguínea , Boston , Dieta , Grasas de la Dieta/administración & dosificación , Ingestión de Energía , Heterocigoto , Homocigoto , Humanos , Estilo de Vida , Persona de Mediana Edad , Puerto Rico/etnología , Circunferencia de la CinturaRESUMEN
BACKGROUND AND AIMS: Using a genetic predisposition score (GPS), integrating the additive associations of a set of single nucleotide polymorphisms (SNPs) with CHD, we examined the consequences of the joint presence of a high GPS and conventional risk factors (CRFs). METHODS AND RESULTS: We studied 11 SNPs at eight loci in 197 participants with prior CHD and 524 CHD-free subjects from the Boston Puerto Rican Health Study. Each polymorphism contributed 1 unit (high-risk allele homozygous), 0.5 units (heterozygous) and 0 units (low-risk allele homozygous) to the GPS. Odds ratio (OR) of CHD for those at high risk because of GPS (>5) and simultaneous presence of CRFs were estimated, compared with subjects at low risk, for both measurements. The mean score was higher in participants with prior CHD than those CHD-free (P=0.015), and the OR for CHD with a GPS>5 was 2.90 (P<0.001).The joint presence of a high GPS and each CRF was associated with higher risk of CHD. Compared to participants with high GPS, those with low GPS (Asunto(s)
Enfermedad Coronaria/genética
, Predisposición Genética a la Enfermedad
, Hispánicos o Latinos/genética
, Anciano
, Consumo de Bebidas Alcohólicas/epidemiología
, Boston
, Enfermedad Coronaria/epidemiología
, Ejercicio Físico
, Femenino
, Frecuencia de los Genes
, Genotipo
, Homocigoto
, Humanos
, Hiperlipidemias/epidemiología
, Hipertensión/epidemiología
, Masculino
, Persona de Mediana Edad
, Oportunidad Relativa
, Polimorfismo de Nucleótido Simple/genética
, Puerto Rico/etnología
, Factores de Riesgo
, Fumar/epidemiología
RESUMEN
To test whether plasma lipoprotein levels and low density lipoprotein (LDL) particle size are modulated by an interaction between habitual saturated fat intake and apolipoprotein E (APOE) genotype, we studied 420 randomly selected free-living Costa Ricans. The APOE allele frequencies were 0.03 for APOE2, 0.91 for APOE3, and 0.06 for APOE4. The median saturated fat intake, 11% of energy, was used to divide the population into two groups, LOW-SAT (mean intake 8.6% energy) represents those below median intake, and HIGH-SAT (mean intake 13.5%) represents those above median intake. Significant interactions between APOE genotype and diet were found for VLDL (P = 0.03) and HDL cholesterol (P = 0.02). Higher saturated fat intake was associated with higher VLDL cholesterol (+29%) and lower HDL cholesterol (-22%) in APOE2 carriers, while the opposite association was observed in APOE4 carriers (-31% for VLDL cholesterol and +10% for HDL cholesterol). Higher saturated fat intake was associated with smaller LDL particles (-2%, P < 0.05) in APOE2 carriers, and larger LDL particles (+2%, P < 0.05) in APOE4 carriers, but the gene-diet interaction was not statistically significant (P = 0.09). Higher saturated fat intake was associated with higher LDL cholesterol in all genotypes (mean +/- SEM, LOW-SAT 2.61 +/- 0.05 vs. HIGH-SAT 2.84 +/- 0.05 mmol/L, P = 0.009). These data suggest that the APOE2 allele could modulate the effect of habitual saturated fat on VLDL cholesterol and HDL cholesterol in a population with an average habitual total fat intake of less than 30%.
Asunto(s)
Apolipoproteínas E/genética , Colesterol/sangre , Grasas de la Dieta , Conducta Alimentaria , Polimorfismo Genético , Adulto , Análisis de Varianza , Colesterol/genética , LDL-Colesterol/sangre , LDL-Colesterol/genética , Costa Rica , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The apolipoprotein E4 allele is associated in industrialized countries with an elevated LDL cholesterol concentration and an increased cardiovascular risk. Our purpose in this study was to assess the influence of the genetic variation at the APOE gene locus on the lipid profile of a Native American rural population. We examined plasma lipid levels and the common apo E alleles in 142 healthy randomly selected adults living in their native communities in western Mexico. Their age was 38+/-17 years and the BMI 25.7+/-4.5 kg/m2. Plasma cholesterol, triglycerides, LDL C and HDL C were 165+/-29.6, 126+/-83, 98+/-26 and 42+/-12.7 mg/dl respectively. Ninety-one per cent of the subjects had Lp(a) concentrations below 20 mg/dl and 30% had levels lower than 2 mg/dl. The most common APOE genotype was E3/3 (63%), followed by E3/4 (30.1%). The prevalence of the E2 allele was very low (2.3%). No difference was observed in LDL C concentrations between the E3/E3 and E3/E4 subjects; however carriers of the E2/3 genotype had lower LDL C levels. Similar results were obtained for cholesterol and apo B levels. In summary, the increased LDL C levels associated with the E4 allele in previous studies were not observed in a population with non-westernized habits. Environmental factors, such as diet and lifestyle, could outweigh the hypercholesterolemic predisposition resulting from the presence of the apo E4 allele.
Asunto(s)
Alelos , Apolipoproteínas E/genética , Indígenas Norteamericanos/genética , Estilo de Vida , Lípidos/sangre , Adulto , Apolipoproteína E4 , Apolipoproteínas E/sangre , Femenino , Genotipo , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/etnología , Hipercolesterolemia/genética , Masculino , México/epidemiología , Distribución Aleatoria , Valores de Referencia , Factores de Riesgo , Población RuralRESUMEN
Coronary heart disease (CHD) is increasing in developing countries, particularly in urban areas. The impact of urbanization and apolipoprotein (apo) A-IV genetic polymorphism on plasma lipoproteins was studied in 222 men and 236 women from rural and urban Costa Rica. The apoA-IV allele frequencies were 0.937 for apoA-IV-1 and 0.062 for apoA-IV-2, Significant interactions between the apoA-IV polymorphism and area of residence (rural versus urban) were detected for HDL cholesterol (P = .003), apoA-I (P = .05), LDL particle size (P = .01), and LDL/HDL cholesterol ratio (P = .005). Urban compared with rural carriers of the apoA-IV-2 allele had significantly lower plasma HDL cholesterol (0.95 versus 1.17 mmol/L) and apoA-I (980 versus 1140 mg/L), a significantly higher LDL/HDL cholesterol ratio (3.35 versus 2.39), and significantly smaller LDL particles (258 versus 263 A). In contrast, no significant rural-urban differences for these parameters were found in apoA-IV-1 homozygotes. Regardless of their apoA-IV phenotype, urban residents consumed more saturated fat (P = .02) and smoked more cigarettes per day (P = .03) than rural residents. A significant interaction between saturated fat intake and apoA-IV phenotype was found for HDL cholesterol (P < .0003) and LDL/HDL cholesterol ratio (P < .003). Increased saturated fat intake (13.6% versus 8.6% of calories) was significantly associated with 6% higher HDL cholesterol and no change (0.7%) in LDL/HDL cholesterol ratio in apoA-IV-1 homozygotes and with 19% lower HDL cholesterol and 37% higher LDL/HDL cholesterol ratio among carriers of the apoA-IV-2 allele. Smokers (> or = 1 cigarette per day) had significantly lower HDL cholesterol (P < .005) and apoA-I (P < .01) concentrations than nonsmokers (< 1 cigarette per day), particularly among carriers of the apoA-IV-2 allele (-19% and -13%) compared with apoA-IV-1 (-4% for both). After taking these lifestyle characteristics into account, the areas of residence by phenotype interactions for plasma lipoprotein concentrations were no longer statistically significant. Lifestyles associated with an urban environment, such as increased smoking and saturated fat intake, elicit a more adverse plasma lipoprotein profile among Costa Rican carriers of the apoA-IV-2 allele than in apoA-IV-1 homozygotes. Therefore, under the conditions studied, persons with the apoA-IV-2 allele may be more susceptible to CHD.
Asunto(s)
Apolipoproteínas A/genética , Arteriosclerosis/etiología , Enfermedad Coronaria/etiología , Adulto , Alelos , Costa Rica , Dieta , Femenino , Heterocigoto , Homocigoto , Humanos , Masculino , Polimorfismo Genético , Factores de Riesgo , Población Rural , Población UrbanaRESUMEN
BACKGROUND: Coronary artery disease (CAD) is becoming more prevalent in developing countries, particularly in the urban areas, in contrast to the CAD mortality trends observed in some industrialized nations. METHODS AND RESULTS: We determined the prevalence of cardiovascular risk factors (hypertension, diabetes, smoking, obesity, total cholesterol greater than or equal to 240 mg/dl and greater than or equal to 200 less than or equal to 239 mg/dl, low density lipoprotein (LDL) cholesterol greater than or equal to 160 mg/dl and greater than 130 less than or equal to 159 mg/dl, and high density lipoprotein (HDL) cholesterol less than 35 mg/dl) in 222 men and 243 women from rural and urban areas of Puriscal, Costa Rica, using the American Cholesterol Education Program guidelines. Urban Puriscal men had a significantly (p less than 0.05) higher prevalence of borderline high-risk total cholesterol (26% versus 14%), borderline high-risk LDL cholesterol (21% versus 11%), smoking (32% versus 13%), and higher prevalence of low HDL cholesterol (34% versus 24%), hypertension (16% versus 13%), diabetes (4.5% versus 2.7%), obesity (21% versus 14%), and saturated fat intake greater than 15% of calories (14% versus 7%) than rural men from Puriscal. No significant differences between rural and urban women were found for any of the cardiovascular risk factors. Urban Puriscal residents were also more sedentary than rural Puriscal residents. CONCLUSIONS: These data indicate that modifiable risk factors are more prevalent in urban than in rural Puriscal, Costa Rica, particularly in men.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Salud Rural , Salud Urbana , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Costa Rica/epidemiología , Complicaciones de la Diabetes , Grasas de la Dieta/efectos adversos , Femenino , Humanos , Hipertensión/complicaciones , Estilo de Vida , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Factores de RiesgoRESUMEN
Increased general and abdominal obesity has been independently associated with diabetes, increased risk of stroke, and coronary artery disease (CAD). It is more prevalent in developed countries and in urban areas of nonindustrialized nations than in less developed and rural areas. To evaluate the associations between general and abdominal obesity (as determined by total body fat, waist to hip ratio, umbilical to triceps ratio, and umbilical to subscapular ratio) with glucose, plasma lipoproteins, apolipoprotein (apo) A-I and B concentrations, and low density lipoprotein (LDL) particle size (LDL 1-7), we randomly selected 222 men and 243 women from rural and urban areas of Puriscal, Costa Rica. Abdominal obesity, as assessed by the waist to hip ratio, was independently and significantly associated with higher triglyceride levels (p less than 0.01) and with lower high density lipoprotein cholesterol levels (p less than 0.05) in men and women and with higher glucose levels (p less than 0.05) and smaller LDL particle size (p less than 0.01) in women. Abdominal obesity, as assessed by the umbilical to subscapular ratio, was independently and significantly associated with higher total cholesterol (p less than 0.005) and apo B (p less than 0.01) levels. Umbilical to triceps ratio was positively associated with blood pressure in men. Urban men had increased general and abdominal obesity (p less than 0.0001), number of cigarettes smoked per day (p less than 0.0001), and diastolic blood pressure (p less than 0.05) and had a decreased fitness level (p less than 0.0001) as well as higher (p less than 0.05) plasma glucose, triglyceride, and total cholesterol concentrations and lower (p less than 0.05) apo A-I and HDL cholesterol levels compared with rural men. The differences between rural and urban women were not as striking. Urban women had increased general and abdominal obesity, glucose, and apo B levels (p less than 0.05) and a decreased fitness level (p less than 0.0001). Our data indicate that general and abdominal obesity, increased cigarette smoking, diastolic blood pressure, and decreased fitness level are more prevalent in an urban than in a rural area in Costa Rica, particularly in men. The higher prevalence of such risk factors in the urban area is associated with a more atherogenic plasma lipoprotein profile.
Asunto(s)
Apolipoproteínas/sangre , Índice de Masa Corporal , Enfermedad Coronaria/epidemiología , Lipoproteínas/sangre , Aptitud Física , Adulto , Anciano , Arteriosclerosis/sangre , Arteriosclerosis/complicaciones , Glucemia/análisis , Enfermedad Coronaria/etiología , Costa Rica/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Factores de Riesgo , Población Rural , Fumar , Triglicéridos/sangre , Población UrbanaRESUMEN
To assess cross-cultural relations between dietary intake and plasma lipoproteins, we randomly selected 222 men and 243 women from the urban and rural areas of Puriscal, Costa Rica; related their dietary composition (assessed by a food-frequency questionnaire), fitness level, and body fat to plasma lipids, apolipoproteins, and low density lipoprotein (LDL) particle size; and compared these data with those from a subsample of 280 adults from the Framingham Offspring Study. Total cholesterol and LDL cholesterol levels were significantly (p less than 0.0001) higher in Framingham (207 and 137 mg/dl, respectively) than in Puriscal (184 and 114 mg/dl, respectively) residents. Elevated triglyceride and apolipoprotein (apo) B levels (25% and 16% higher), low HDL cholesterol and apo A-I levels (12% and 29% lower), and smaller LDL particles (17%) were more frequent in Puriscal than in Framingham residents. Urban Puriscal residents had a significantly lower fitness level; increased body fat, total cholesterol, and triglyceride levels; decreased HDL cholesterol in men; and higher apo B levels in women compared with rural Puriscal residents. Body fat, animal fat, and saturated fat intakes were significantly correlated with total cholesterol, LDL cholesterol, and apo B levels in both men and women in Puriscal. Intakes of protein and animal fat were higher among urban (10.7% and 14.1%, respectively) compared with rural (8.9% and 9.9%, respectively) Puriscal residents and in Framingham (16.0% and 20.8%, respectively) compared with Puriscal residents. No significant differences were found in dietary cholesterol. Saturated fat (largely from palm oil in Puriscal) intakes were significantly different among the three groups: rural Puriscal, 10.7% of calories; urban Puriscal, 11.6%; and Framingham residents, 12.9%. These data indicate that the more atherogenic plasma lipid profile among urban compared with Puriscal residents was largely explained by increased adiposity, decreased fitness level, and higher saturated fatty acid intake. Puriscal residents consumed less animal fat and more carbohydrate than did Framingham residents, and these differences were associated with a 21% lower LDL cholesterol level, a 12% lower HDL cholesterol level, a 29% lower apo A-I level, a 25% higher triglyceride level, a 16% higher apo B level, and a 17% smaller LDL particle size. Some of these cross-cultural differences may be due to differences in ethnic background and physical activity as well.