Sequence variation in the soluble epoxide hydrolase gene and subclinical coronary atherosclerosis: interaction with cigarette smoking.
Soluble epoxide hydrolase (EPHX2) catalyses the degradation of the vasoactive and anti-inflammatory epoxyeicosatrienoic acids and may play a role in the pathophysiology of atherosclerosis. 1337 African-Americans and 1645 Whites from the CARDIA study were genotyped for 22 and 15 EPHX2 single nucleotide polymorphisms (SNPs), respectively, to examine the associations of common EPHX2 haplotypes and genotypes with presence of coronary artery calcified plaque (CAC). The potential influence of cigarette smoking, which increases EPHX2 gene expression, on these associations was also assessed. In African-Americans, a common haplotype uniquely tagged by the R287Q polymorphism was associated with significantly greater risk for CAC (OR=1.7; 95% CI=1.04-3.0). In Whites, a common haplotype uniquely tagged by a polymorphism in Intron 11 of the gene was associated with significantly greater risk for CAC (OR=1.3; 95% CI=1.02-1.6). These haplotype-tagging polymorphisms also showed significant associations with CAC in individual SNP analyses, and these relationships were significantly modified by smoking. This detailed investigation of the association of EPHX2 genetic variation with CAC supports EPHX2's emerging role as a risk factor for atherosclerosis, whose effects are influenced by smoking.
Wei
Qi
Q
Institute of Molecular Medicine, University of Texas Health Science Center-Houston, Houston, TX 77030, United states.
Doris
Peter A
PA
Pollizotto
Martin V
MV
Boerwinkle
Eric
E
Jacobs
David R
DR
Siscovick
David S
DS
Fornage
Myriam
M
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D003324:Coronary Artery Disease / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D012995:Solubility; D044465:White People / Q000706:statistics & numerical data
D004851:Epoxide Hydrolases; C506428:EPHX2 protein, human