Association of gene polymorphisms with coronary artery disease in individuals with or without nonfamilial hypercholesterolemia.
A substantial proportion of individuals with coronary artery disease (CAD) has concomitant hypercholesterolemia. A large-scale association study was performed to identify separately genes that confer susceptibility to CAD in the absence or presence of nonfamilial hypercholesterolemia. The study population comprised 5248 unrelated Japanese individuals, including 3085 subjects with CAD (2350 men, 735 women) and 2163 controls (1329 men, 834 women). Among all study subjects, 2541 individuals (1688 men, 853 women) had nonfamilial hypercholesterolemia, and 2707 individuals (1991 men, 716 women) did not have this condition. The genotypes for 33 polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hyperuricemia revealed that three polymorphisms [994G --> T (Val279Phe) in the platelet-activating factor acetylhydrolase gene, 242C --> T (His72Tyr) in the NADH/NADPH oxidase p22 phox gene, and 1100C --> T in the apolipoprotein C-III gene] were significantly associated with CAD in men with hypercholesterolemia. Genotyping of these three polymorphisms may prove informative for prediction of the genetic risk for CAD in men with nonfamilial hypercholesterolemia.
Shimokata
Keiko
K
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yamada
Yoshiji
Y
Kondo
Takahisa
T
Ichihara
Sahoko
S
Izawa
Hideo
H
Nagata
Kohzo
K
Murohara
Toyoaki
T
Ohno
Miyoshi
M
Yokota
Mitsuhiro
M
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009252:NADPH Dehydrogenase / Q000235:genetics*; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase