Association of the AGXT2 V140I polymorphism with risk for coronary heart disease in a Chinese population.
OBJECTIVE
Asymmetric dimethylarginine (ADMA) is a nitric oxide synthase (NOS) inhibitor that decreases NO production and promotes the development of cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) plays an important role in ADMA metabolism. This study was designed to explore the association of the AGXT2 V140I (rs37369 G＞A) polymorphism with risk for coronary heart disease (CHD) in a Chinese population.


METHODS
A case-control study including 1103 controls and 942 CHD patients was performed. The patients were genotyped for rs37369 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma ADMA concentration in healthy controls was measured by an enzyme-linked immunosorbent assay (ELISA).


RESULTS
The rs37369 GG genotype was significantly overrepresented in CHD patients compared to the controls (18.5% versus 14.8%, p=0.025), and it was significantly associated with increased risk for CHD in smokers (OR=2.21, 95% CI: 1.24-3.92, p=0.007) and marginally increased CHD risk for individuals with diabetes mellitus (OR=1.92; 95% CI: 0.94-3.91, p=0.074). The association between rs37369 and CHD risk was further increased in smokers with diabetes mellitus (OR=3.32, 95% CI:1.14-9.67, p=0.028). Patients who smoked and were rs37369 GG homozygous showed significantly higher plasma ADMA levels than carriers of the rs37369 A allele (p=0.004). However, in non-smokers, patients homozygous for rs37369 GG showed significantly lower plasma ADMA concentrations than carriers of the rs37369 A allele (p=0.003). Furthermore, smokers homozygous for rs37369 GG showed significantly higher plasma ADMA concentrations than non-smokers with the same genotype (p=0.012).


CONCLUSIONS
The AGXT2 rs37369 polymorphism is associated with increased risk for CHD in smokers and in diabetes mellitus patients. This increased risk may be due to increased plasma ADMA levels.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University.
Ji-Peng
JP
Zhou
Yong-Ping
YP
Bai
Xiao-Lei
XL
Hu
Da-Bin
DB
Kuang
Rui-Zheng
RZ
Shi
Yan
Y
Xiong
Wei
W
Zhang
Jian
J
Xia
Bi-Lian
BL
Chen
Tian-Lun
TL
Yang
Xiao-Ping
XP
Chen
D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China; D003327:Coronary Disease / Q000150:complications / Q000235:genetics*; D017931:DNA Primers; D048909:Diabetes Complications; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012907:Smoking; D000637:Transaminases / Q000235:genetics*
D017931:DNA Primers; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase