ABSTRACT
BACKGROUND: A polymorphism in a gene may exert its effects on multiple phenotypes. The aim of this study is to explore the association of 10 metabolic syndrome candidate genes with excess weight and adiposity and evaluate the effect of perinatal and socioeconomic factors on these associations. METHODS: The anthropometry, socioeconomic and perinatal conditions and 10 polymorphisms were evaluated in 1081 young people between 10 and 18 years old. Genotypic associations were calculated using logistic and linear models adjusted by age, gender, and pubertal maturation, and a genetic risk score (GRS) was calculated by summing the number of effect alleles. RESULTS: We found that AGT-rs699 and the IRS2-rs1805097 variants were significantly associated with excess weight, OR = 1.25 (CI 95% 1.01-1.54; p = 0.034); OR = 0.77 (CI 95% 0.62-0.96; p = 0.022), respectively. AGT-rs699 and FTO-rs17817449 variants were significantly and directly associated with body mass index (BMI) (p = 0.036 and p = 0.031), while IRS2-rs1805097 and UCP3-rs1800849 were significantly and negatively associated with BMI and waist circumference, correspondingly. Each additional effect allele in GRS was associated with an increase of 0.020 log(BMI) (p = 0.004). No effects from the socioeconomic and perinatal factors evaluated on the association of the candidate genes with the phenotypes were detected. CONCLUSIONS: Our observation suggests that AGT-rs699 and FTO-rs17817449 variants may contribute to the risk development of excess weight and an increase in the BMI, while IRS2-rs1805097 showed a protector effect; in addition, UCP3- rs1800849 showed a decreasing waist circumference. Socioeconomic and perinatal factors had no effect on the associations of the candidate gene.
ABSTRACT
Introducción. La hipertensión arterial es una enfermedad multifactorial influenciada por componentes genéticos y ambientales, cuya prevalencia varía entre grupos étnicos. Se han llevado a cabo numerosos estudios en genes de sistemas reguladores de la presión arterial, como el sistema renina-angiotensinaaldosterona, el sistema nervioso simpático, los factores endoteliales, y el balance de sodio, mostrando resultados incongruentes entre poblaciones. Objetivos. Evaluar el efecto de variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 y del componente ancestral individual, sobre la hipertensión arterial y las cifras de presión arterial en una muestra de población antioqueña. Materiales y métodos. Se genotipificaron 107 casos y 253 controles para 12 variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 , y para 20 marcadores informativos de ascendencia. Se evaluó la asociación de los polimorfismos y sus interacciones, y de la composición genética ancestral con hipertensión y cifras de presión arterial. Resultados. Los genes ADD2 , rs4852706 (OR=3,0; p=0,023); DRD1 , rs686 (OR=0,38; p=0,012) y ADRB2 , rs1042718 (OR=10,0; p=0,008); y combinaciones genotípicas de DRD1 con AGTR1 ; de AGT con ADD1 ; y de ADD1 con ATP2B1 y PTGS2 , se asociaron con hipertensión arterial. El componente ancestral amerindio se asoció con disminución en la presión arterial diastólica. Conclusiones. Variantes en los genes ADD2 , DRD1 , ADRB2 , AGTR1 , AGT , ADD1 , ATP2B1 y PTGS2 , individualmente o en su interacción, se encuentran asociadas con hipertensión. El componente ancestral amerindio tiene un efecto sobre las cifras de presión arterial.
Introduction: Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations. Objectives: To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia. Methods and materials: 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined. Results: Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure. Conclusion: Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Hypertension/genetics , Angiotensinogen/genetics , Blood Pressure/genetics , Calmodulin-Binding Proteins/genetics , Colombia , /genetics , Peptidyl-Dipeptidase A/genetics , Plasma Membrane Calcium-Transporting ATPases/genetics , Receptor, Angiotensin, Type 1/genetics , /genetics , Receptors, Dopamine D1/genetics , /genetics , Risk FactorsABSTRACT
INTRODUCTION: Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations. OBJECTIVES: To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia. METHODS AND MATERIALS: 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined. RESULTS: Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure. CONCLUSION: Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.
Subject(s)
Hypertension/genetics , Adult , Angiotensinogen/genetics , Blood Pressure/genetics , Calmodulin-Binding Proteins/genetics , Colombia , Cyclooxygenase 2/genetics , Female , Humans , Male , Middle Aged , Peptidyl-Dipeptidase A/genetics , Plasma Membrane Calcium-Transporting ATPases/genetics , Receptor, Angiotensin, Type 1/genetics , Receptors, Adrenergic, beta-2/genetics , Receptors, Dopamine D1/genetics , Receptors, Thromboxane A2, Prostaglandin H2/genetics , Risk FactorsABSTRACT
Colombia is a country with great geographic heterogeneity and marked regional differences in pre-Columbian native population density and in the extent of past African and European immigration. As a result, Colombia has one of the most diverse populations in Latin America. Here we evaluated ancestry in over 1,700 individuals from 24 Colombian populations using biparental (autosomal and X-Chromosome), maternal (mtDNA), and paternal (Y-chromosome) markers. Autosomal ancestry varies markedly both within and between regions, confirming the great genetic diversity of the Colombian population. The X-chromosome, mtDNA, and Y-chromosome data indicate that there is a pattern across regions indicative of admixture involving predominantly Native American women and European and African men.
Subject(s)
Genetic Markers/genetics , Genetics, Population/methods , Racial Groups/genetics , Chromosomes, Human, X/genetics , Chromosomes, Human, Y/genetics , Colombia , DNA, Mitochondrial/genetics , Female , Geography , Haplotypes/genetics , Humans , Male , Sex FactorsABSTRACT
INTRODUCTION: The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance. OBJECTIVE: The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus. MATERIALS AND METHODS: In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 informative markers for European, African and Amerind ancestry. RESULTS: Association between type 2 diabetes mellitus and the polymorphisms 3826A (OR=0.78; 95% CI = 0.63-0.97; p = 0.02) and 55 C (OR = 1.41; 95% CI = 1.04-1.92; p = 0.03) and the haplotype D45, 866G, 1957G, 2723T, and 55C (OR = 1.26; 95% CI = 1.02-1.56; p = 0.03) were found. These associations remained after adjustment using individual genetic admixture estimates. CONCLUSION: Some alleles of uncoupling protein genes 1, 2 and 3, and their haplotypes confer risk to type 2 diabetes in a northwestern Colombian population.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Ion Channels/genetics , Mitochondrial Proteins/genetics , Adult , Aged , Alleles , Black People/genetics , Colombia/epidemiology , Confounding Factors, Epidemiologic , Diabetes Mellitus, Type 2/ethnology , Ethnicity/genetics , Female , Haplotypes/genetics , Humans , Indians, South American/genetics , Male , Marriage , Middle Aged , Mutation, Missense , Odds Ratio , Polymorphism, Single Nucleotide , Spain/ethnology , Uncoupling Protein 1 , Uncoupling Protein 2 , Uncoupling Protein 3ABSTRACT
Introducción. Las proteínas desacoplantes pertenecen a la familia de proteínas transportadoras de aniones que desacoplan la producción de ATP de la respiración mitocondrial, causando pérdida de protones a través de la membrana mitocondrial interna y disipando la energía en forma de calor. Aunque su función no ha sido bien establecida, algunos polimorfismos en estas proteínas se han asociado con diabetes mellitus tipo 2, obesidad y resistencia a la insulina. Objetivo. Evaluar la asociación entre las variantes -3826A/G, ID 45, -2723T/A, -1957G/A, -866G/A, -55C/T de los genes de las proteínas desacoplantes 1, 2 y 3 con diabetes mellitus tipo 2 en una población del nordeste colombiano. Materiales y métodos. Se tipificaron 545 casos y 449 controles para 14 variantes de los genes de las proteínas desacoplantes por medio de PCR y PCR-RFLP. Se hicieron pruebas de asociación simples con ji al cuadrado y se corrigieron en un análisis de regresión logística bayesiana, incluyendo los estimados de mezcla individual obtenidos mediante 54 marcadores informativos de ascendencia europea, africana y amerindia. Resultados. Las variantes -3826A (OR=0,78; IC95% 0,63-0,97; p=0,02), -55C (OR=1,41; IC95% 1,04-1,92; p=0,03) de las proteínas desacoplantes 1 y 3, respectivamente, y el haplotipo D45, -866G, -1957G, -2723T, -55C (OR=1,26; IC95% 1,02-1,56; p=0,03) se asociaron con diabetes tipo 2. Estas asociaciones se conservaron después de ajustar por la mezcla genética individual. Conclusión. Algunas variantes de las proteínas desacoplantes 1, 2 y 3, y sus haplotipos, confieren riesgo para diabetes mellitus tipo 2 en una población del nordeste colombiano.
Introduction. The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance. Objective. The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus. Materials and methods. In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 informative markers for European, African and Amerind ancestry. Results. Association between type 2 diabetes mellitus and the polymorphisms 3826A (OR=0.78; 95%CI=0.63-0.97; p=0.02) and 55C (OR=1.41; 95%CI=1.04-1.92; p=0.03) and the haplotype D45, 866G, 1957G, 2723T, and 55C (OR=1.26; 95%CI=1.02-1.56; p=0.03) were found. These associations remained after adjustment using individual genetic admixture estimates. Conclusion. Some alleles of uncoupling protein genes 1, 2 and 3, and their haplotypes confer risk to type 2 diabetes in a northwestern Colombian population.
Subject(s)
Diabetes Mellitus/genetics , Genotype , Haplotypes , Insulin Resistance , ObesityABSTRACT
El objetivo de la investigación fue identificar en pacientes con diagnóstico presuntivo de MELAS la mutación A3243G, tradicionalmente asociada con ella. Se secuenciaron los fragmentos 533 pb del genoma mitocondrial correspondiente al tRNA-Leu y parte del gen NDI (posiciones 3162 a 3695) en 29 pacientes con diagnóstico presuntivo de MELAS y en cuatro personas sanas. Todos los pacientes fueron negativos para la mutación A3243G, tampoco se hallaron otras mutaciones descritas en MELAS. Se halló una transición (A3547G) en el gen NDI, hasta ahora no informada en la literatura, en 14 de las muestras secuenciadas. Esta transición, identificada en pacientes y controles, cambia el codón ATC(i) por GTC(V). Al realizar el genotipo del mtDNA de la PCR, se encontró que de las 14 muestras con G en la posición 3547 de NDI, 13 expresaban el haplotipo B. Teniendo en cuenta que la transición detectada se presentó tanto en pacientes como en controles y que I y V son aminoácidos de estructura química semejante, hidrofóbicos, que se localizan en un motivo altamente hidrofóbico de la proteína (LALTIALLL), es posible concluír que este cambio consiste en un polimorfismo. La presencia del Haplotipo B, propia de la población amerindia, indica la alta frecuencia de mitocondria de origen antioqueño. La transición 3547G podría ser un marcador de la población indoamericana con la cual se mezclaron los españoles para constituír la población antioqueña
