Analysis of additive effects of common functional variants of candidate genes on the risk for coronary artery diseases

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Coronary artery disease (CAD) is a common multifactorial disease. Dyslipidemia and hypertension are important risk factor for CAD. At first we have screened the common functional variants in the candidate genes for dyslipidemia and hypertension. We have found that a Val227Ala polymorphism in peroxisome proliferator activated receptor α gene is associated with variations in serum lipid levels, and a Lys528Arg polymorphism in adipocyte-derived leucine aminopeptidase gene is associated with blood pressure. But we could not found the associations between such polymorphisms and CAD.Furthermore, we have investigated the relationship between the functional variants of 11 candidate genes for CAD (APOE, MTHFR, AGT, ACE, LPA, HTT, LIPC, ADRB3, LPL, PAI1, ENOS) and CAD. Among of them, the significant associations with CAD were observed in the variants of APOE, LPA, and MTHFR. Additive effects of the variants of these three genes on the risk for CAD were investigated. The odds ratio for the risk of CAD associated with each variant ranged from 1.4 to 1.9. The odds ratio associated with the presence of two variant genes were 3.5. These data suggest that combined and additive effects of common functional variants of several candidate genes may be an important genetic factor for CAD.