Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population.
Coronary atherosclerosis is a complex and progressive condition that involves many biological pathways, including the oxidative stress and inflammatory response pathways. To investigate the association between common genetic variation within these two pathways and coronary atherosclerosis, we performed a comprehensive two-stage candidate gene association study in a Chinese Han population. In stage I, 936 tag single-nucleotide polymorphisms (SNPs) within 116 candidate genes were genotyped in 293 coronary atherosclerosis cases and 293 age- and gender-matched healthy controls. In stage II, 51 SNPs from stage I were selected and further genotyped in an additional 1030 cases and 764 controls. In allele- and genotype-based association tests of stage II and a meta-analysis across the two stages, we identified three SNPs within three genes significantly associated with the disease, namely rs3212556 in ITGA2 (P(CMH)=9.20 x 10(-5)), rs854563 in PON1 (P(CMH)=1.92 x 10(-4)) and rs9283851 in THBS2 (P(CMH)=3.00 x 10(-3)). Haplotype analysis provided further supporting evidence for the association of rs3212556 (P(global)<10(-4)) and rs854563 (P(global)<10(-4)). Our study has identified three SNPs within ITGA2, PON1 and THBS2 that are associated with coronary atherosclerosis.
Wang
Ying
Y
Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Fu
Wenqing
W
Xie
Fang
F
Wang
Yi
Y
Chu
Xun
X
Wang
Haifeng
H
Shen
Min
M
Wang
Ying
Y
Wang
Yi
Y
Sun
Weiwei
W
Lei
Rong
R
Yang
Lin
L
Wu
Hong
H
Foo
Jianee
J
Liu
Jianjun
J
Jin
Li
L
Huang
Wei
W
D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D019699:Thrombospondins / Q000235:genetics*; D000099262:Thrombospondin 2
D043303:Aryldialkylphosphatase; D039421:Integrin alpha2; D019699:Thrombospondins; D000099262:Thrombospondin 2; C468406:PON1 protein, human