Genetic factors in coronary artery disease in women

Coronary artery disease (CAD), a major cause of the mortality and morbidity in industrialized countries, is a multifactorial disease caused by the interactions of multigenic inheritance and environmental factors. CAD is a major public health problem in the United States. In addition to the known environmental factors, it is important to understand the role of the multigenic make-up that affects the pathogenesis of CAD. The candidate gene approach has led to the identification of a large set of genes, which may be involved in determining interindividual differences in the distribution of biological traits that are risk factors for developing CAD. Among these candidate genes, the genes participating in lipoprotein metabolisms have been studied most extensively. Other genes that are not directly involved in lipid metabolism, but are functionally related to CAD pathology, are also important to be examined for their contribution to the progression of CAD. The objective of this study was to evaluate the role of genetic variation in several candidate genes in relation to CAD. The selected genes include, apolipoprotein A-V (APOA-V), apolipoprotein E (APOE), apolipoprotein H (APOH, β2-glycoprotein 1), oxidized LDL-receptor-1 (OLR1, LOX-1), LDL-receptor related protein1 (LRP1), lipoprotein lipase (LPL), hepatic lipase (HL), cholesteryl ester transfer protein (CETP), and paraoxonase (PON1 and PON2). We found that the APOE (p = 0.0001), OLR1/3 ′UTR (p = 0.015), OLR1/intron 5 (p = 0.011), OLR1/intron 4 (p = 0.011), PON1/codon 192 (p = 0.033) and PON2/codon 311 (p = 0.038) polymorphisms were significantly associated with the risk of CAD. We also observed significant interactions between smoking × APOA-V*T, family history of CAD × APOE*4, BMI × APOH 247/TT, age × APOH 316/GC, LDL-cholesterol × LRP1/codon 216/TC, and smoking × LPL/codon 447*X in whites; family history of CAD × LPL/Hind III *G, and diabetes × PON1 55/Met in blacks. The genetic variations in the APOE, CETP, HL, LPL and PON genes were also significantly associated with plasma lipid profile. Our data suggest that common genetic variation in the candidate gene may modify the risk of CAD.