Population structure from NOS genes correlates with geographical differences in coronary incidence across Europe.

OBJECTIVES: The population analysis of cardiovascular risk and non-risk genetic variation can help to identify adaptive or random demographic processes that shaped coronary incidence variation across geography. MATERIAL AND METHODS: In this study, 114 single nucleotide polymorphisms and 17 tandem repeat polymorphisms from Nitric Oxide Synthases (NOS) regions were analyzed in 1686 individuals from 35 populations from Europe, North Africa, and the Middle East. NOS genes encode for key enzymes on nitric oxide availability, which is involved in several cardiovascular processes. These genetic variations were used to test for selection and to infer the population structure of NOS regions. Moreover, we tested whether the variation in the incidence of coronary events and in the levels of classical risk factors in 11 of these European populations could be explained by the population structure estimates. RESULTS: Our results supported, first, the absence of clear signs of selection for NOS genetic variants associated with cardiovascular diseases, and second, the presence of a continuous genetic pattern of variation across European and North African populations without a Mediterranean barrier for gene flow. Finally, population structure estimates from NOS regions are closely correlated with coronary event rates and classical risk parameters (explaining 39-98%) among European populations. CONCLUSION: Our results reinforce the hypothesis that genetic bases of cardiovascular diseases and associated complex phenotypes could be geographically shaped by random demographic processes.

Association between rs2200733 and rs7193343 genetic variants and atrial fibrillation in a Spanish population, and meta-analysis of previous studies.

INTRODUCTION AND OBJECTIVES: The objectives of this study were to analyze the association between two genetic variants (rs2200733 and rs7193343) in a Spanish population and the risk of developing atrial fibrillation, and to carry out a systematic review and meta-analysis of these associations. METHODS: We performed a case-control study involving 257 case patients with atrial fibrillation and 379 controls. The case patients were individuals who had donated samples to the Spanish National DNA Bank; the controls were participating in a population-based cross-sectional study. Genotyping was carried out using a TaqMan assay. We conducted a systematic literature search in which 2 independent reviewers extracted the necessary information. The study involved a meta-analysis, a heterogeneity analysis, and a meta-regression analysis to identify the variables that explain the heterogeneity across studies. RESULTS: In our population, the presence of atrial fibrillation was found to be associated with rs2200733 (odds ratio = 1.87; 95% confidence interval, 1.30-2.70), but not with rs7193343 (odds ratio = 1.18; 95% confidence interval, 0.80-1.73). In the meta-analysis, we observed an association between atrial fibrillation and both variants: odds ratio = 1.71 (95% confidence interval, 1.54-1.90) for rs2200733 and odds ratio = 1.18 (95% confidence interval, 1.11-1.25) for rs7193343. We observed heterogeneity among the studies dealing with the association between rs2200733 and atrial fibrillation, partially related to the study design, and the strength of association was greater in case-control studies (odds ratio = 1.83) than in cohort studies (odds ratio = 1.41). CONCLUSIONS: Variants rs2200733 and rs7193343 are associated with a higher risk of atrial fibrillation. Case-control studies tend to overestimate the strength of association between these genetic variants and atrial fibrillation.

Asociación de los polimorfismos rs2200733 y rs7193343 con la fibrilación auricular en población española y metanálisis de la evidencia existente / Association Between rs2200733 and rs7193343 Genetic Variants and Atrial Fibrillation in a Spanish Population, and Meta-analysis of Previous Studies

Introducción y objetivos Los objetivos del estudio son analizar en población española la asociación entre dos variantes genéticas (rs2200733 y rs7193343) y el riesgo de sufrir fibrilación auricular y realizar una revisión sistemática y un metanálisis de estas asociaciones. Métodos Estudio de casos y controles con 257 casos de fibrilación auricular y 379 controles. Los casos eran donantes del Banco Nacional de ADN; los controles participaron en un estudio transversal de base poblacional. La genotipificación se realizó mediante pruebas TaqMan. Se realizó una búsqueda bibliográfica sistemática, dos revisores independientes extrajeron la información necesaria. Se realizó un metanálisis, un análisis de heterogeneidad y de metarregresión para identificar las variables que explicaran la heterogeneidad entre estudios. Resultados En nuestra población se observa una asociación entre el rs2200733 y la presencia de fibrilación auricular (odds ratio = 1,87; intervalo de confianza del 95%, 1,30-2,70), pero no con el rs7193343 (odds ratio = 1,18; intervalo de confianza del 95%, 1,11-1,25) para el rs7193343. En la asociación entre el rs2200733 y la fibrilación auricular se observó heterogeneidad entre estudios, parcialmente relacionada con el diseño del estudio, con mayor magnitud de asociación en estudios de casos y controles (odds ratio = 1,83) que en cohortes (odds ratio = 1,41). Conclusiones: Las variantes rs2200733 y rs7193343 se asocian con mayor riesgo de fibrilación auricular. Los estudios de casos y controles tienden a sobrestimar la magnitud de la asociación entre estas variantes genéticas y la fibrilación auricular

Introduction and objectives The objectives of this study were to analyze the association between two genetic variants (rs2200733 and rs7193343) in a Spanish population and the risk of developing atrial fibrillation, and to carry out a systematic review and meta-analysis of these associations. Methods We performed a case-control study involving 257 case patients with atrial fibrillation and 379 controls. The case patients were individuals who had donated samples to the Spanish National DNA Bank; the controls were participating in a population-based cross-sectional study. Genotyping was carried out using a TaqMan assay. We conducted a systematic literature search in which 2 independent reviewers extracted the necessary information. The study involved a meta-analysis, a heterogeneity analysis, and a meta-regression analysis to identify the variables that explain the heterogeneity across studies. Results In our population, the presence of atrial fibrillation was found to be associated with rs2200733 (odds ratio = 1.87; 95% confidence interval, 1.30-2.70), but not with rs7193343 (odds ratio = 1.18; 95% confidence interval, 0.80-1.73). In the meta-analysis, we observed an association between atrial fibrillation and both variants: odds ratio = 1.71 (95% confidence interval, 1.54-1.90) for rs2200733 and odds ratio = 1.18 (95% confidence interval, 1.11-1.25) for rs7193343. We observed heterogeneity among the studies dealing with the association between rs2200733 and atrial fibrillation, partially related to the study design, and the strength of association was greater in case-control studies (odds ratio = 1.83) than in cohort studies (odds ratio = 1.41). Conclusions: Variants rs2200733 and rs7193343 are associated with a higher risk of atrial fibrillation. Case-control studies tend to overestimate the strength of association between these genetic variants and atrial fibrillation