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Breast cancer (BCa) is the most common type of cancer affecting women worldwide. Some histological subtypes of benign breast disease (BBD) are considered risk factors for developing BCa. Single nucleotide polymorphisms (SNPs) in the genes encoding apolipoproteins A-I (APOA1) and B (APOB) have been associated with BCa in Tunisian, Chinese, and Taiwanese populations. The objective of this pilot study is to evaluate the possible contribution of APOA1 and APOB polymorphisms to BCa and BBD in the Mexican population. We analyzed the association of 4 SNPs in genes encoding apolipoproteins: rs670 and rs5069 in the APOA1 gene, and rs693 and rs1042031 in the APOB gene, by performing PCR-RFLP with DNA extracted from the biopsy tissue of Mexican women with BCa or BBD and whole blood samples obtained from the general population (GP). Our results showed an association between the CT + TT genotypes of the SNP rs5069 and BBD (p = 0.03201). In the A-T haplotype, the frequency of the SNPs rs670 and rs5069 differed significantly between the BBD group and the GP and BCa groups (p = 0.004111; p = 0.01303). In conclusion, the SNP rs5069 is associated with BBD but not with BCa in the Mexican population.
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Neoplasias de la Mama , Polimorfismo de Nucleótido Simple , Apolipoproteína A-I/genética , Apolipoproteínas B/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Femenino , Haplotipos , Humanos , Proyectos Piloto , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
OBJECTIVE: To estimate the correlation between indices of diet quality (DQIs), insulin sensitivity (QUICKI) and resistance (HOMA-IR), waist circumference (WHR) and body mass (BMI) and the alleles and genotypes of the TJP1 SNP rs2291166 and the VNTR of ATXN2 in adolescent patients. SUBJECTS AND METHOD: The study enrolled 85 subjects aged 10-20years, from the city of Tuxtepec, Oaxaca, Mexico, recruited in the period 2017-2018. DQIs, BMI, WHR, HOMA-IR, QUICKI, and diet quality index were measured. The rs2291166 polymorphism in TJP1 was determined by allele-specific PCR and the (CAG)n expansion in ATXN2 was determined by hot start PCR. PCR products were analyzed using 8% PAGE electrophoresis and silver nitrate staining. RESULTS: A correlation was found of indices DQIs, HOMA-IR, WHR and BMI with the heterozygous genotype of the TJP1 SNP rs2291166 and the long and short repeats of the ATXN2 CAG repeat in obese adolescent patients. A very strong positive correlation was seen between the TJP1 SNP and the HOMA-IR index (P<.05). A positive correlation was also found between the ATXN2 CAG repeat and the QUICKI index (P=.000) (P<.05), while the DQIs index correlated more closely with BMI and WHR. CONCLUSIONS: DQIs, TJP1 SNP rs2291166, and ATXN2 CAG repeat are determinants of obesity-related risk parameters such as BMI, WHR, QUICKI, and HOMA-IR in the adolescent population analyzed.
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INTRODUCTION: Introduction: breast milk (MH) contains nutrients and bioactive compounds for child development, including probiotic bacteria, which contribute to intestinal maturation. This benefit accompanies the individual until adulthood. There are new methods such as spray drying that give this compound a good conservation without loss of microbiota. Objective: the aim of this study was to analyze the viability of lactic acid bacteria isolated from human milk with probiotic potential after the spray drying process, as well as to evaluate the possible adhesion in the colon of mice of the Balb/C strain after feeding them powdered human milk and a commercial formula milk. Method: we isolated and identified the presence of lactic acid bacteria with possible probiotic potential in powdered human milk using the MALDI-TOF MS technique. Powdered human milk and a commercial formula milk were fed to mice of the Bald/C strain for 14 weeks. Glucose level and weight were measured in the mice. The feces were collected to verify the presence of lactic bacteria. The mice were sacrificed and their intestines were weighed, isolating the lactic acid bacteria both from the intestines and from the feces. The strains isolated from mice fed human milk were evaluated for their probiotic potential, analyzing their ability to inhibit pathogens, resistance to pH, temperature, adhesion, and hydrophobicity. Results: the presence of Lactobacillus fermentum LH01, Lactobacillus rhamnosus LH02, Lactobacullis reuteri LH03, and Lactobacillus plantarum LH05 in powdered human milk was identified. All strains showed a possible probiotic profile due to the ability of bacteria to resist low pH, bile salts, and exposure to gastric enzymes, as well as their hydrophobicity and self-aggregation capacity, and their failure to show hemagglutination or hemolysis activity in a culture medium rich in erythrocytes. We observed that the consumption of powdered human milk prevented weight gain and constipation in mice. Conclusions: after spray drying, strains with possible probiotic potential may be preserved in human milk. The consumption of powdered human milk with probiotic bacteria prevents constipation and weight gain in mice, when compared to those fed a commercial formula milk.
INTRODUCCIÓN: Introducción: la leche materna (HM) contiene los nutrientes y compuestos bioactivos necesarios para el desarrollo infantil, incluidas bacterias probióticas, que contribuyen a la maduración intestinal. Objetivo: el objetivo de este estudio fue analizar la viabilidad de las bacterias acidolácticas aisladas de la leche humana con potencial probiótico, después del proceso de secado, así como evaluar su posible adhesión en el colón de ratones (BAlb/C) alimentados con leche humana en polvo y leche de una fórmula comercial. Método: se aislaron e identificaron mediante la técnica de Maldi-Tof-MS las bacterias acidolácticas con posible potencial probiótico en la leche humana en polvo. Se alimentó con leche humana en polvo y leche de una fórmula comercial a ratones de la cepa Bald/C durante 14 semanas. Se midieron el nivel de glucosa y el peso. Las heces se recolectaron para verificar la presencia de bacterias lácticas. Los ratones se sacrificaron y se pesaron los intestinos, aislando las bacterias lácticas tanto de los intestinos como de las heces. En las cepas aisladas de la leche humana se evaluó el potencial probiótico analizando su capacidad para inhibir patógenos, resistir distintos pH y temperaturas, adherirse y mostrar hidrofobicidad. Resultados: se identificó la presencia de Lactobacillus fermentum LH01, Lactobacillus rhamnosus LH02, Lactobacullis reuteri LH03 y L. plantarum LH05 en la leche humana en polvo. Todas las cepas mostraron resistencia a los pH bajos, a las sales biliares y a la exposición a enzimas gástricas, así como una buena hidrofobicidad y capacidad de autoagregación. Además, no presentaron actividad de hemaglutinación o hemólisis en un medio de cultivo rico en eritrocitos. Observamos que el consumo de leche humana en polvo evita en los ratones el aumento de peso y el estreñimiento. Conclusiones: después del secado por aspersión, las cepas con posible potencial probiótico pueden conservarse en la leche materna. El consumo de leche humana en polvo con bacterias probióticas evita el estreñimiento y el aumento de peso en los ratones, en comparación con los alimentados con leche de una formula comercial.
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Lactobacillales/fisiología , Leche Humana/microbiología , Probióticos , Secado por Pulverización , Animales , Fenómenos Fisiológicos Bacterianos , Glucemia/análisis , Peso Corporal , Heces/microbiología , Humanos , Intestinos/microbiología , Lactobacillales/aislamiento & purificación , Limosilactobacillus fermentum/aislamiento & purificación , Limosilactobacillus fermentum/fisiología , Lactobacillus plantarum/aislamiento & purificación , Lactobacillus plantarum/fisiología , Limosilactobacillus reuteri/aislamiento & purificación , Limosilactobacillus reuteri/fisiología , Lacticaseibacillus rhamnosus/aislamiento & purificación , Lacticaseibacillus rhamnosus/fisiología , Masculino , México , Ratones , Ratones Endogámicos BALB C , PolvosAsunto(s)
Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Macrófagos/efectos de los fármacos , Monocitos/efectos de los fármacos , Primer Trimestre del Embarazo/sangre , Tercer Trimestre del Embarazo/sangre , Receptores de Superficie Celular/sangre , Adulto , Antígeno B7-2/sangre , Estradiol/sangre , Femenino , Humanos , Hidrocortisona/sangre , Interleucina-10/sangre , Interleucina-1beta/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Receptores de Lipopolisacáridos/sangre , Lipopolisacáridos/farmacología , Embarazo , Progesterona/sangre , Prolactina , Células THP-1RESUMEN
Introducción: Los pacientes con artritis reumatoide pueden desarrollar enfermedad tiroidea autoinmune (ETA), cuyo diagnóstico clínico puede ser difícil debido a que ambas comparten síntomas como artralgias, mialgias, rigidez matutina o fatiga. Objetivo: Determinar la prevalencia de ETA en pacientes con artritis reumatoide. Método: Estudio transversal que incluyó 78 pacientes con artritis reumatoide y 81 controles clínicamente sanos pareados por edad y sexo. A ambos grupos se realizó cuantificación de anticuerpos antitiroideos, pruebas de función tiroidea, ultrasonido y biopsia de glándula tiroides cuando la puntuación de Thyroid Imaging Reporting and Data System (TIRADS) fue ≥ 4. Resultados: 24.4 % de los pacientes con artritis reumatoide presentó hipotiroidismo (p = 0.003) y altos títulos de anticuerpos antitiroideos versus controles clínicamente sanos; 53 % de los ultrasonidos tiroideos resultó normal en pacientes hipotiroideos; en pacientes con artritis reumatoide positivos para anticuerpos antitiroideos se encontró perfusión incrementada en 40 %. Los casos clasificados como TIRADS 4 fueron enviados a aspiración, con resultado histopatológico benigno. Conclusiones: Se demostró el valor clínico agregado de la evaluación tiroidea en pacientes con artritis reumatoide, conforme a la prevalencia de hipotiroidismo subclínico, positividad de anticuerpos antitiroideos y anomalías en el ultrasonido independientes de la función tiroidea normal o alterada. Introduction: Patients with rheumatoid arthritis can develop autoimmune thyroid disease (ATD), the clinical diagnosis of which can be difficult because both entities share symptoms such as arthralgia, myalgia, morning stiffness or fatigue. Objective: To determine the prevalence of ATD in patients with rheumatoid arthritis. Method: Cross-sectional study that included 78 patients with rheumatoid arthritis and 81 clinically healthy controls matched by age and gender. Both groups underwent anti-thyroid antibodies quantification, thyroid function tests, thyroid ultrasound and thyroid gland biopsy when the Thyroid Imaging Reporting and Data System (TIRADS) score was ≥ 4. Results: Hypothyroidism was found in 24.4% of patients with rheumatoid arthritis (p = 0.003), as well as high titers of anti-thyroid antibodies versus clinically healthy controls; 53% of thyroid ultrasounds were normal in hypothyroid patients, and increased perfusion was found in 40% of rheumatoid arthritis patients who tested positive for anti-thyroid antibodies. Cases classified as TIRADS 4 underwent aspiration with benign histopathological results. Conclusions: Thyroid assessment added clinical value was demonstrated in patients with rheumatoid arthritis, according to the prevalence of subclinical hypothyroidism, anti-thyroid antibodies positivity and ultrasound abnormalities, regardless of normal or altered thyroid function.
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Artritis Reumatoide/fisiopatología , Hipotiroidismo/epidemiología , Tiroiditis Autoinmune/epidemiología , Ultrasonografía/métodos , Adulto , Autoanticuerpos/inmunología , Biopsia , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Pruebas de Función de la Tiroides , Tiroiditis Autoinmune/diagnóstico , Tiroiditis Autoinmune/diagnóstico por imagenRESUMEN
B7H6, an endogenous ligand expressed on tumor cell surfaces, triggers NKp30-mediated activation of human NK cells. In contrast, the release of soluble B7H6 has been proposed as a novel mechanism by which tumors might evade NK cell-mediated recognition. Since NK cells are critical for the maintenance of early pregnancy, it is not illogical that soluble B7H6 might also be an important factor in directing NK cell activity during normal pregnancy. Thus, this study was focused on the characterization of soluble B7H6 during the development of normal pregnancy. Serum samples were obtained from healthy pregnant women who were experiencing their second pregnancies (n=36). Additionally, 17 of these pregnant participants were longitudinally studied for the presence of B7H6 during their second and third trimesters. Age-matched healthy non-pregnant women served as controls (n=30). The presence of soluble B7H6 was revealed by Western blotting. A further characterization was performed using an immunoproteomic approach based on 2DE-Western blotting combined with MALDI-MS. The results show that sera from all pregnant women were characterized by the presence of two novel isoforms of B7H6, both with lower MW than the reported of 51kDa. These isoforms were either a heavy (â¼37kDa) or a light isoform (â¼30kDa) and were mutually exclusive. N-glycosylation did not completely explain the different molecular weights exhibited by the two isoforms, as was demonstrated by enzymatic deglycosylation with PNGase F. The confirmation of the identity and molecular mass of each isoform indicates that B7H6, while maintaining the C- and N-termini, is most likely released during pregnancy by a mechanism distinct from proteolytic cleavage. We found that both isoforms, but mainly the heavier B7H6, were released via exosomes; and that the lighter isoform was also released in an exosome-free manner that was not observed in the heavy isoform samples. In conclusion, we find that soluble B7H6 is constitutively expressed during pregnancy and that, moreover, the soluble B7H6 is present in two new isoforms, which are released by exosomal and exosome-free mechanisms.
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Antígenos B7/sangre , Exosomas/metabolismo , Células Asesinas Naturales/inmunología , Receptor 3 Gatillante de la Citotoxidad Natural/agonistas , Isoformas de Proteínas/genética , Antígenos B7/genética , Femenino , Regulación de la Expresión Génica , Glicosilación , Humanos , Activación de Linfocitos , Embarazo , Tercer Trimestre del EmbarazoRESUMEN
PURPOSE: Antinuclear autoantibodies (ANA) targeting the dense fine speckled antigen DFS70, also known as lens epithelium-derived growth factor p75 (LEDGF/p75), are attracting attention due to their low frequency in systemic rheumatic diseases but increased frequency in clinical laboratory referrals and healthy individuals (HI). These ANA specifically recognize the stress protein DFS70/LEDGFp75, implicated in cancer, HIV-AIDS, and inflammation. While their frequency has been investigated in various ethnic populations, there is little information on their frequency among Hispanics/Latinos. In this study, we determined the frequency of anti-DFS70/LEDGFp75 autoantibodies in Mexican Hispanics using multiple detection platforms. METHODS: The frequency of anti-DFS70/LEDGFp75 antibodies was determined in 171 individuals, including 71 dermatomyositis (DM) patients, 47 rheumatoid arthritis (RA) patients, 30 obesity (OB) patients, and 23 HI. Antibody detection was achieved using four complementary assay platforms: indirect immunofluorescence, Western blotting, ELISA, and chemiluminescent immunoassay. RESULTS: We detected relatively low frequencies of anti-DFS70/LEDGFp75 antibodies in patients with DM (1.4%), RA (4.3%), and OB (6.6%), and elevated frequency (17.4%) in HI. A strong concordance between the different antibody detection platforms was observed. CONCLUSIONS: The low frequency of anti-DFS70/LEDGFp75 antibodies in Mexican patients with rheumatic diseases, but relatively higher frequency in HI, is consistent with previous observations with non-Hispanic populations, suggesting that geographic differences or ethnicity do not influence the frequency of these autoantibodies. Our results also highlight the importance of confirmatory assays for the accurate detection of these autoantibodies. Future studies with larger cohorts of healthy Hispanics/Latinos are needed to confirm if their anti-DFS70/LEDGFp75 antibody frequencies are significantly higher than in non-Hispanics.
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OBJECTIVE: The aim of this study was to investigate the main factors associated to a diminished health-related quality of life (HRQoL) evaluated by INCAVISA (Health-Related Quality of Life Inventory for Latin American Patients) in patients with rheumatoid arthritis (RA). METHODS: Female, 18 years or older, RA (American College of Rheumatology 1987 criteria and American College of Rheumatology/European League against Rheumatism 2010 criteria) patients who attended the outpatient rheumatology department of the Hospital Civil "Dr. Juan I. Menchaca," Guadalajara, Mexico, matched with healthy controls were included. Patients with any known comorbidities or treatment with antidepressive drugs were excluded. Trained physicians performed the RA clinical evaluation and INCAVISA. All data were analyzed using SPSS 21.0 software (SPSS Inc, Chicago, IL); P < 0.05 was considered statistically significant. RESULTS: Patients with polypharmacy (≥3 drugs) had a lower HRQoL by INCAVISA. The number of drugs, total comorbidities, and DAS-28 (Disease Activity Score on 28 Joints) were negatively correlated with total INCAVISA. In multivariate analysis, DAS-28 and polypharmacy were independent predictors for a negative perception of HRQoL evaluated by INCAVISA in RA patients. CONCLUSIONS: Disease activity and disability secondary to RA have a negative impact in the HRQoL. Other factors such as the number of drugs prescribed to these patients have been shown to be important for the negative perception of their HRQoL evaluated by INCAVISA.
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Artritis Reumatoide/tratamiento farmacológico , Polifarmacia , Adolescente , Adulto , Anciano , Chicago , Femenino , Humanos , México , Persona de Mediana Edad , Calidad de Vida , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Genetic susceptibility has been described in insulin resistance (IR). Chemokine (C-C motif) ligand-2 (CCL2) is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2). The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2), metabolic markers, and adiposity. In a cross-sectional study we included 380 Mexican-Mestizo individuals, classified with IR according to Stern criteria. Polymorphism was identified using PCR-RFLP/sequence-specific primers. Anthropometrics and metabolic markers were measured by routine methods and adipokines and sCCL2 by ELISA. The CCL2 polymorphism was associated with IR (polymorphic A+ phenotype frequencies were 70.9%, 82.6%, in individuals with and without IR, resp.). Phenotype carriers CCL2 (A+) displayed lower body mass and fat indexes, insulin and HOMA-IR, and higher adiponectin levels. Individuals with IR presented higher sCCL2 compared to individuals without IR and was associated with CCR2 (Ile+) phenotype. The double-polymorphic phenotype carriers (A+/Ile+) exhibited higher sCCL2 than double-wild-type phenotype carriers (A-/Ile-). The present findings suggest that sCCL2 production possibly will be associated with the adiposity and polymorphic phenotypes of CCL2 and CCR2, in Mexican-Mestizos with IR.
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Adiposidad , Quimiocina CCL2/sangre , Resistencia a la Insulina/etnología , Polimorfismo Genético , Receptores CCR2/sangre , Adulto , Anciano , Antropometría , Quimiocina CCL2/genética , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Asociación Genética , Humanos , Resistencia a la Insulina/genética , Masculino , México , Persona de Mediana Edad , Obesidad/etnología , Obesidad/genética , Fenotipo , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Receptores CCR2/genética , Adulto JovenAsunto(s)
Inmunosupresores , Miositis , Tuberculosis del Sistema Nervioso Central , Tuberculosis Cutánea , Tuberculosis Osteoarticular , Adulto , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Administración del Tratamiento Farmacológico , México/epidemiología , Persona de Mediana Edad , Miositis/diagnóstico , Miositis/tratamiento farmacológico , Miositis/etiología , Prevalencia , Estudios Retrospectivos , Ajuste de Riesgo , Factores de Riesgo , Prevención Secundaria , Tuberculosis del Sistema Nervioso Central/complicaciones , Tuberculosis del Sistema Nervioso Central/tratamiento farmacológico , Tuberculosis del Sistema Nervioso Central/epidemiología , Tuberculosis Cutánea/complicaciones , Tuberculosis Cutánea/tratamiento farmacológico , Tuberculosis Cutánea/epidemiología , Tuberculosis Osteoarticular/complicaciones , Tuberculosis Osteoarticular/tratamiento farmacológico , Tuberculosis Osteoarticular/epidemiologíaRESUMEN
The aim of this study was to investigate the relationship between functional polymorphisms Gly482Ser in PPARGC1A and Pro12Ala in PPARG2 with the presence of obesity and metabolic risk factors. We included 375 individuals characterized as Mexican-Mestizos and classified by the body mass index (BMI). Body dimensions and distribution of body fat were measured. The HOMA-IR and adiposity indexes were calculated. Adipokines and metabolic profile quantification were performed by ELISA and routine methods. Genetic polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism analysis. A difference between obese and nonobese subjects in polymorphism PPARGC1A distribution was observed. Among obese individuals, carriers of genotype 482Gly/Gly were observed to have decreased body fat, BMI, and body fat ratio versus 482Ser/Ser carriers and increased resistin and leptin levels in carriers Gly+ phenotype versus Gly- phenotype. Subjects with PPARG2 Ala- phenotype (genotype 12Pro/Pro) showed a decreased HOMA-IR index versus individuals with Ala+ phenotype (genotypes 12Pro/Ala plus 12Ala/Ala). We propose that, in obese Mexican-Mestizos, the combination of alleles 482Ser in PPARGC1A and 12Pro in PPARG2 represents a reduced metabolic risk profile, even when the adiposity indexes are increased.
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Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/genética , Obesidad/epidemiología , Obesidad/genética , PPAR gamma/genética , Factores de Transcripción/genética , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Estudios de Asociación Genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Humanos , Incidencia , Masculino , México/etnología , Persona de Mediana Edad , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Distribución por Sexo , Adulto JovenRESUMEN
The polymorphisms in leptin (LEP G-2548A) and leptin-receptor (LEPR Gln223Arg) seem to influence obesity and lipid metabolism among others. The aim of this study was to investigate the effect of these polymorphisms on adiposity, leptin (sLeptin), and leptin-receptor (sLeptin-receptor) serum concentrations as well as inflammation markers. We included 382 adults originally from Western Mexico. They were genotyped by PCR-RFLP. Obese individuals showed higher sLeptin (58.2 ± 31.35 ng/mL) but lower sLeptin-receptor (12.6 ± 3.74 ng/mL) levels than normal weight ones (17.6 ± 14.62 ng/mL, 17.4 ± 4.62 ng/mL, resp.), P < 0.001. Obese subjects carriers of Arg/Arg genotype had more (P = 0.016) sLeptin-receptor (14.7 ± 4.96 ng/mL) and less (P = 0.004) sLeptin (44.0 ± 28.12 ng/mL) levels than Gln/Gln genotype (11.0 ± 2.92 ng/mL, 80.3 ± 33.24 ng/mL, resp.). Body fat mass was lower (P from 0.003 to 0.045) for A/A (36.5% ± 6.80) or Arg/Arg (36.8% ± 6.82) genotypes with respect to G/G (41.3% ± 5.52) and G/A (41.6% ± 5.61) or Gln/Gln (43.7% ± 4.74) and Gln/Arg (41.0% ± 5.52) genotypes carriers. Our results suggest that LEP -2548A and LEPR 223Arg could be genetic markers of less body fat mass accumulation in obese subjects from Western Mexico.
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Predisposición Genética a la Enfermedad , Leptina/genética , Obesidad/genética , Receptores de Leptina/genética , Adiposidad/genética , Adulto , Índice de Masa Corporal , Femenino , Genotipo , Humanos , Leptina/sangre , Metabolismo de los Lípidos/genética , Masculino , Americanos Mexicanos , México , Persona de Mediana Edad , Obesidad/sangre , Obesidad/patología , Polimorfismo de Nucleótido Simple , Receptores de Leptina/sangreRESUMEN
UNLABELLED: The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. METHODS: Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P < 0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P < 0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P = 0.02). The cIMT correlated with levels of anti-CCP (r = 0.513, P = 0.001), CRP (r = 0.799, P < 0.001), TNFα (r = 0.642, P = 0.001), and IL-6 (r = 0.751, P < 0.001). In multiple regression analysis, cIMT was associated with CRP (P < 0.001) and anti-CCP levels (P = 0.03). CONCLUSIONS: Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events.
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Artritis Reumatoide/sangre , Proteína C-Reactiva/metabolismo , Enfermedades de las Arterias Carótidas/sangre , Interleucina-6/sangre , Péptidos Cíclicos/sangre , Factor de Necrosis Tumoral alfa/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/epidemiología , Aterosclerosis/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades de las Arterias Carótidas/epidemiología , Grosor Intima-Media Carotídeo/estadística & datos numéricos , Estudios de Cohortes , Comorbilidad , Estudios Transversales , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
UNLABELLED: Patients with rheumatoid arthritis (RA) have a higher risk for atherosclerosis. There is no clinical information about scavenger receptor CD36 and the development of subclinical atherosclerosis in patients with RA. The aim of this study was to evaluate the association between membrane expression of CD36 in peripheral blood mononuclear cells (PBMC) and carotid intima-media thickness (cIMT) in patients with RA. METHODS: We included 67 patients with RA from the Rheumatology Department of Hospital Civil "Dr. Juan I. Menchaca," Guadalajara, Jalisco, Mexico. We evaluated the cIMT, considering subclinical atherosclerosis when >0.6 mm. Since our main objective was to associate the membrane expression of CD36 with subclinical atherosclerosis, other molecules related with cardiovascular risk such as ox-LDL, IL-6, and TNFα were tested. RESULTS: We found low CD36 membrane expression in PBMC from RA patients with subclinical atherosclerosis (P < 0.001). CD36 mean fluorescence intensity had negative correlations with cIMT (r = -0.578, P < 0.001), ox-LDL (r = -0.427, P = 0.05), TNFα (r = -0.729, P < 0.001), and IL-6 (r = -0.822, P < 0.001). CONCLUSION: RA patients with subclinical atherosclerosis showed low membrane expression of CD36 in PBMC and increased serum proinflammatory cytokines. Further studies are needed to clarify the regulation of CD36 in RA.
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Artritis Reumatoide/sangre , Artritis Reumatoide/complicaciones , Aterosclerosis/sangre , Aterosclerosis/complicaciones , Antígenos CD36/sangre , Monocitos/metabolismo , Adulto , Grosor Intima-Media Carotídeo , Membrana Celular/metabolismo , Estudios Transversales , Femenino , Humanos , Interleucina-6/sangre , Masculino , México , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/sangreRESUMEN
INTRODUCTION: Insulin resistance (IR) is a disease with genetic susceptibility characterized by the increase in storage and irregular body fat distribution, and impaired production of adipokines. OBJECTIVE: The objective was to investigate the relationship between 3'UTR+62G>A RETN gene polymorphism, with adiponectin-resistin index (ARindex), adiposity, and inmuno-metabolic markers. METHODS: In this cross-sectional study, 260 individuals characterized as Mexican-Mestizo and classified in lean and overweight, and IR and without-IR, were included. Anthropometrics, body composition, body fat distribution and inflammation and metabolic markers were measured by routine methods, RETN 3'UTR+62G>A alleles were identified by PCR-RFLP and soluble insulin, total adiponectin and resistin were measured by ELISA methods. RESULTS: The +62G allele frequencies for lean and overweight individuals were different P=0.0343 (95.4% and 98.4%, respectively). The lean GA genotype carriers showed significant low measures of ARindex, adiposity, and inmuno-metabolic markers, than the GG genotype carriers. We found differences between individuals with IR and without-IR: in ARindex (P=0.002), adiponectin (P=0.002) and resistin levels (P=0.033): 1.102 ± 0.03, 5.167 ± 0.36 ug/mL and 8.827 ± 0.42 ng/mL versus 1.336 ± 0.07, 3.577 ± 0.34 ug/mL and 10.480 ± 0.65 ng/mL. Showed correlations with inflammation markers, distribution and body fat storage (r=0.262 to 0.414), P< 0.05. CONCLUSIONS: The present data suggest that in a Mexican-mestizo population the RETN +62G>A polymorphism is associated with overweight. The presence of the +62A allele was associated with increase of total adiponectin, ARindex, resistin levels, metabolic markers and body fat storage. ARindex can be an early indicator of insulin resistance.
Introducción: La resistencia a la insulina (RI) se caracteriza por susceptibilidad genética, incremento en la adiposidad y distribución irregular de grasa corporal, con alteración en la producción de adipocinas. Objetivo: Investigar la asociación del polimorfismo 3'UTR+62G>A en resistina con RI, índice adiponectina-resistina (ARindex), adiposidad y marcadores inmuno-metabólicos. Métodos: En un estudio transversal a 260 mestizos-mexicanos, clasificados con peso normal, exceso de peso, sin y con RI, se les evaluó: composición corporal, distribución de masa grasa y marcadores inmuno-metabólicos. Los alelos del polimorfismo 3'UTR+62G>A en resistina se identificaron por PCR-RFLP. La concentración sérica de insulina, adiponectina total y resistina se midieron por la técnica de ELISA. Resultados: Las frecuencias del alelo +62G para los individuos con peso normal y exceso de peso, fueron (95.4% y 98.4%, respectivamente) P=0.0343. Los portadores del genotipo GA con peso normal mostraron valores menores del ARindex, adiposidad y marcadores inmuno-metabólicos comparados con los portadores del genotipo GG. Se observó diferencia entre los individuos sin y con RI en el ARindex (P=0.002), concentración sérica de adiponectina (P=0.002) y resistina (P=0.033): 1.102±0.03, 5.167±0.36ug/mL y 8.827±0.42ng/mL versus 1.336±0.07, 3.577±0.34ug/mL y 10.480±0.65ng/mL, respectivamente. Los marcadores inmuno-metabólicos, reserva y distribución de grasa corporal correlacionan con ARindex (r=0.262 a 0.414), PA en los individuos mestizos-mexicanos con exceso de peso. El alelo +62A se asoció con incremento de adiponectina total, valores menores del ARindex, concentración de resistina, marcadores metabólicos y reserva de grasa corporal. El ARindex puede ser un indicador temprano de RI.
Asunto(s)
Regiones no Traducidas 3'/genética , Adiponectina/sangre , Adiposidad/genética , Resistencia a la Insulina/genética , Resistina/genética , Adulto , Anciano , Estudios Transversales , Femenino , Frecuencia de los Genes , Humanos , Indígenas Centroamericanos , Masculino , México/epidemiología , Persona de Mediana Edad , Polimorfismo Genético , Resistina/sangre , Adulto JovenRESUMEN
PURPOSE: Obesity is a disease with genetic susceptibility characterized by an increase in storage and irregular distribution of body fat. In obese patients, the decrease in the Adiponectin gene (ADIPOQ) expression has been associated with a systemic low-grade inflammatory state. Our aim was to investigate the relationship between ADIPOQ +45T>G gene simple nucleotide polymorphism (SNP rs2241766) with serum adiponectin (sAdiponectin), distribution of body fat storage, and inflammation markers. SUBJECTS AND METHODS: In this cross-sectional study, 242 individuals from Western Mexico characterized as Mexican-Mestizo and classified by body mass index (BMI), were included. Anthropometrics, body composition, body fat distribution, and inflammation markers were measured by routine methods. Genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and sAdiponectin by the ELISA method. A P-value <0.05 was considered the statistically significant threshold. RESULTS: sAdiponectin is associated with BMI (P < 0.001) and the genotypes (P < 0.001 to 0.0046) GG (8169 ± 1162 ng/mL), TG (5189 ± 501 ng/mL), and TT (3741 ± 323 ng/mL), but the SNP ADIPOQ +45T>G is not associated with BMI. However, the detailed analysis showed association of this SNP with a pattern of fat distribution and correlations (P < 0.05) with inflammation markers and distribution of body fat storage (Pearson's r = -0.169 to -0.465) were found. CONCLUSION: In this study, we have suggested that the ADIPOQ +45G allele could be associated with distribution of body fat storage in obesity. On the other hand, as no association was observed between ADIPOQ +45T>G gene polymorphism and obesity, it cannot be concluded that the ADIPOQ +45G allele is responsible for the increase of adiponectin levels.
RESUMEN
INTRODUCTION: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The PTPN22 gene encodes lymphoid tyrosine phosphatase LYP, a potent negative regulator of T cell activation. Polymorphic variants of this gene have previously been associated with various autoimmune disorders. The +1858C/T single-nucleotide polymorphism (SNP) (rs2476601), in the exon 14 of the PTPN22 gene has been associated with susceptibility to RA in several population. OBJECTIVE: The aim of this work was to investigate whether the +1858C/T of the PTPN22 gene is associated with susceptibility to RA in Western Mexico population. METHODS: A total of 309 unrelated RA patients, classified according to American College of Rheumatology (ACR) 1987 criteria, as well as 347 controls residents from Western Mexico were recruited for this study. The DNA samples were genotyped for +1858C/T PTPN22 gene SNP using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The frequency of +1858T risk allele was significantly increased in patients with RA compared with controls (p=0.001, OR=2.83, 95%CI=1.50-5.32). To confirm this results we established a comparison between subjects carrying of CT+TT genotypes versus those carrying CC genotype, between both groups (p=0.004, OR=2.65, 95%CI=1.33-5.36). Nevertheless, we not observed association of the +1858C/T PTPN22 gene SNP with clinical activity and functional disability in RA patients. Likewise, the +1858T variant in RA patients seropositive for anti-CCP antibodies, increased the risk for RA (p=0.008, OR=2.5, 95%CI=1.3-5.0) when we compared with controls; however, in the group of seronegative patients, no was found significant difference (p=0.1, OR=2.5, 95%CI=0.9-7.2). CONCLUSIONS: Our results support the association of the +1858T risk allele of the +1858C/T PTPN22 polymorphism with susceptibility to RA and confirm that, in combination with anti-CCP antibodies, this SNP influence the autoimmune processes towards a development of RA in Mexican population.
Asunto(s)
Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Artritis Reumatoide/diagnóstico , Autoanticuerpos/sangre , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , México , Persona de Mediana Edad , Adulto JovenRESUMEN
Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, cartilage and bone. PAI-1 is a key regulator of the fibrinolytic system through which plasminogen is converted to plasmin. The plasmin activates the matrix metalloproteinase system, which is closely related with the joint damage and bone destruction in RA. The aim of this study was to investigate the relationship between 4G/5G PAI-1 polymorphism with mRNA expression and PAI-1 plasma protein levels in RA patients. 113 RA patients and 123 healthy subjects (HS) were included in the study. The 4G/5G PAI-1 polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism method; the PAI-1 mRNA expression was determined by real-time PCR; and the soluble PAI-1 (sPAI-1) levels were quantified using an ELISA kit. No significant differences in the genotype and allele frequencies of 4G/5G PAI-1 polymorphism were found between RA patients and HS. However, the 5G/5G genotype was the most frequent in both studied groups: RA (42%) and HS (44%). PAI-1 mRNA expression was slightly increased (0.67 fold) in RA patients with respect to HS (P = 0.0001). In addition, in RA patients, the 4G/4G genotype carriers showed increased PAI-1 mRNA expression (3.82 fold) versus 4G/5G and 5G/5G genotypes (P = 0.0001), whereas the sPAI-1 plasma levels did not show significant differences. Our results indicate that the 4G/5G PAI-1 polymorphism is not a marker of susceptibility in the Western Mexico. However, the 4G/4G genotype is associated with high PAI-1 mRNA expression but not with the sPAI-1 levels in RA patients.
Asunto(s)
Artritis Reumatoide/genética , Inhibidor 1 de Activador Plasminogénico/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Artritis Reumatoide/sangre , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , México , Persona de Mediana Edad , Inhibidor 1 de Activador Plasminogénico/sangre , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unknown etiology. Many cytokines have been found to be associated with RA pathogenesis and among them is macrophage migration inhibitory factor (MIF). The aim of this study was to determine whether MIF serum levels are associated with RA course, clinical activity, and clinical biomarkers of the disease. MIF levels were determined in serum samples of 54 RA patients and 78 healthy subjects (HS) by enzyme-linked immunosorbent assay (ELISA). Disease activity was evaluated using the DAS28 score. Patients were subgrouped according to disease activity and years of evolution of disease. Statistical analysis was carried out by SPSS 10.0 and GraphPad Prism 5 software. RA patients presented increased levels of MIF as compared to HS. MIF levels were raised on early stages of RA and tend to decrease according to years of evolution. Moreover, MIF levels positively correlated with rheumatoid factor in RA patients and with C reactive protein in all individuals studied. Our findings suggest that MIF plays a role in early stages of RA.
Asunto(s)
Artritis Reumatoide/sangre , Oxidorreductasas Intramoleculares/sangre , Factores Inhibidores de la Migración de Macrófagos/sangre , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Pronóstico , Factor Reumatoide/sangre , Índice de Severidad de la Enfermedad , Regulación hacia Arriba , Adulto JovenRESUMEN
Se investigó la relación entre los polimorfismos de E-selectina, la molécula de adhesión vascular-1 (VCAM1) y la molécula de adhesión intercelular-1 (ICAM1) con el perfil de lípidos y marcadores clínicos de inflamación en artritis reumatoide (AR). Se incluyeron 60 pacientes con AR clasificados de acuerdo a los criterios del American College of Rheumatology (ACR, 1987) y 60 controles clínicamente sanos (CCS), no relacionados entre sí, definidos como población de mestizos mexicanos. Los genotipos se caracterizaron por la técnica de PCR-RFLP. La velocidad de sedimentación globular (VSG), factor reumatoideo (FR), concentración de fibrinógeno (FB), proteína C reactiva (PCR) y perfil de lípidos, se realizaron por métodos convencionales. El análisis estadístico se efectuó con SPSS v10.0. La VSG correlacionó con PCR, FR, FB y cHDL, (r=0,507; 0,296; 0,475 y -0,308, respectivamente); PCR con FB (r=0,613), p<0,05. El alelo 1238G se asoció con FR y Apo-B; y el alelo 721A, con cHDL y cLDL (p<0,05). Los datos muestran que los niveles de FB, cHDL, y los alelos 721A de ICAM1 y 1238G de VCAM1 se asocian con los marcadores clínicos de inflamación. Existen diferencias entre la distribución de los polimorfismos en este estudio y las reportadas para población oriental, caucásica y turca.
The genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) technique. The ESR (erythrocyte sedimentation rate), RF (rheumatoid factor), fibrinogen (FB), C-reactive protein (CRP) and lipid profile were measured by routine methods. Statistical analysis was performed using SPSS v10.0. The significant Pearson´s correlations were: ESR with CRP, RF, FB and HDLc, (r=0.507, 0.296, 0.475, and -0.308, respectively); CRP with FB (r=0.613), p<0.05. The results showed an association with A allele of ICAM1 polymorphism and serum levels of HDLc and LDLc; and Apo-B and FR showed an association with C allele of VCAM1 polymorphism (p<0.05). Data shows that FB and HDLc levels, and ICAM1 polymorphism allele 721A and VCAM1 polymorphism allele 1238G are associated with clinical inflammation markers in RA. Our Mexican-mestizo population showed differences with many reports (from English, American, Turkish, Japanese, Chinese, Italian, and Korean populations).