Sequence variation in the soluble epoxide hydrolase gene and subclinical coronary atherosclerosis: Interaction with cigarette smoking

Qi Wei, Peter A. Doris, Martin V. Pollizotto, Eric Boerwinkle, David R. Jacobs, David S. Siscovick, Myriam Fornage

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)26-34
Number of pages9
JournalAtherosclerosis
Volume190
Issue number1
DOIs
StatePublished - Jan 2007

Bibliographical note

Funding Information:
The authors thank the staff and participants of the CARDIA study for their important contributions. This study is supported by grants RO1-NS41466 and RO1-HL69126 to MF and by contracts N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050 and N01-HC-95095 from the National Heart, Lung, and Blood Institute to the CARDIA investigators.

Keywords

  • Atherosclerosis
  • Calcium
  • EPHX2
  • Genetics
  • Smoking

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