Association of putative functional variants in the PLAU gene and the PLAUR gene with myocardial infarction.
uPA (urokinase-plasminogen activator) and its receptor (uPAR) have been implicated in a broad spectrum of pathophysiological processes, including fibrinolysis, proteolysis, inflammation, atherogenesis and plaque destabilization, all of which are involved in the pathogenesis of MI (myocardial infarction). We hypothesized that putative functional genetic variation in the two genes encoding uPA and uPAR (PLAU and PLAUR respectively) might influence the susceptibility to MI. We genotyped rs4065 [3'-UTR (untranslated region) *141C>T) and rs2227564 (Pro141Leu) in the PLAU gene as well as rs344781 (-516T>C) in the PLAUR gene in 633 MI patients and 1237 gender- and age-matched control subjects. Our results showed that the T allele of rs4065 was significantly associated with an increased risk of MI, with an adjusted OR (odds ratio) of 1.38 [95% CI (confidence interval), 1.07-1.78; P=0.012) under the dominant model, 1.4 (95% CI, 1.12-1.75; P=0.003) under the additive model and 2.5 (95% CI, 1.15-5.41; P=0.02) under the recessive model. The findings were then replicated in another independent case-control study including 545 MI patients and 597 control subjects. In conclusion, our results suggest that rs4065 might be a previously unknown genetic risk factor for MI in the Chinese Han population.
FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Jing
J
Xu
Wenlong
W
Li
Xunna
X
Bao
Hu
H
Ding
Jingzhou
J
Chen
Weili
W
Zhang
Kai
K
Sun
Jizheng
J
Wang
Xiaojian
X
Wang
Hu
H
Wang
Hui
H
Yu
Weihua
W
Song
Weiwei
W
Ma
Lin
L
Zhang
Changxin
C
Wang
Daowen
D
Wang
Rutai
R
Hui
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator