The HIF1A rs2057482 polymorphism is associated with risk of developing premature coronary artery disease and with some metabolic and cardiovascular risk factors. The Genetics of Atherosclerotic Disease (GEA) Mexican Study.
The aim of the present study was to establish the role of HIF1A gene polymorphisms in the risk of developing premature coronary artery disease (CAD) in a well-characterized clinical cohort. Three polymorphisms in HIF1A (rs11549465, rs11549467, rs2057482) gene were genotyped in 949 patients with premature CAD, and 676 healthy controls (with negative calcium score by computed tomography). Under a dominant model adjusted for age, visceral to subcutaneous adipose tissue (VAT/SAT) ratio, hypertension, type 2 diabetes mellitus (T2DM), HDL-C levels, hypercholesterolemia and hypertriglyceridemia, the rs2057482 T allele was associated with decreased risk of premature CAD when compared to healthy controls (OR = 0.616, P(dom) = 0.020). The effect of the studied polymorphisms on various metabolic parameters and cardiovascular risk factors was explored. In this analysis, the rs2057482 T allele was associated with decreased risk of obesity, central obesity, hypertension, hypercholesterolemia, hypertriglyceridemia and increased risk of T2DM. Under a dominant model adjusted by age, the HIF1A rs2057482 T polymorphism was associated with high VAT/SAT ratio (P = 0.009) and HDL-C levels (P = 0.04) in healthy controls. The results suggest that HIF1A rs2057482 polymorphism is involved in the risk of developing CAD and is associated with some metabolic parameters and cardiovascular risk factors.
Molecular Synovioanalisis Laboratory, Instituto Nacional de Rehabilitación, Mexico City, Mexico.
Alberto
A
López-Reyes
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
José Manuel
JM
Rodríguez-Pérez
Molecular Synovioanalisis Laboratory, Instituto Nacional de Rehabilitación, Mexico City, Mexico.
Javier
J
Fernández-Torres
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Nancy
N
Martínez-Rodríguez
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Nonanzit
N
Pérez-Hernández
Molecular Synovioanalisis Laboratory, Instituto Nacional de Rehabilitación, Mexico City, Mexico.
Arturo Javier
AJ
Fuentes-Gómez
Molecular Synovioanalisis Laboratory, Instituto Nacional de Rehabilitación, Mexico City, Mexico.
Carlos Alberto
CA
Aguilar-González
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Edith
E
Alvarez-León
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Carlos
C
Posadas-Romero
Genomic Laboratory, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
Teresa
T
Villarreal-Molina
Molecular Synovioanalisis Laboratory, Instituto Nacional de Rehabilitación, Mexico City, Mexico.
Carlos
C
Pineda
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: gvargas63@yahoo.com.
Gilberto
G
Vargas-Alarcón
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
Cardiovascular risk factors; Coronary artery disease; Hypoxia; Hypoxia-inducible factor 1-alpha; Ischemia; Polymorphisms