Association of the AGXT2 V140I Polymorphism with Risk for Coronary Heart Disease in a Chinese Population

Ji-Peng Zhou; Yong-Ping Bai; Xiao-Lei Hu; Da-Bin Kuang; Rui-Zheng Shi; Yan Xiong; Wei Zhang; Jian Xia; Bi-Lian Chen; Tian-Lun Yang; Xiao-Ping Chen

doi:10.5551/jat.23077

Original Article

Association of the AGXT2 V140I Polymorphism with Risk for Coronary Heart Disease in a Chinese Population

Ji-Peng Zhou, Yong-Ping Bai, Xiao-Lei Hu, Da-Bin Kuang, Rui-Zheng Shi, Yan Xiong, Wei Zhang, Jian Xia, Bi-Lian Chen, Tian-Lun Yang, Xiao-Ping Chen

Author information

Ji-Peng Zhou
Department of Clinical Pharmacology, Xiangya Hospital, Central South University
Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics
Yong-Ping Bai
Department of Geriatric Medicine, Xiangya Hospital, Central South University
Xiao-Lei Hu
Department of Clinical Pharmacology, Xiangya Hospital, Central South University
Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics
Da-Bin Kuang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University
Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics
Rui-Zheng Shi
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University
Yan Xiong
Department of Clinical Pharmacology, Xiangya Hospital, Central South University
Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics
Wei Zhang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University
Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics
Jian Xia
Department of Neurology Medicine, Xiangya Hospital, Central South University
Bi-Lian Chen
Department of Geriatric Medicine, Xiangya Hospital, Central South University
Tian-Lun Yang
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University
Xiao-Ping Chen
Department of Clinical Pharmacology, Xiangya Hospital, Central South University
Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics

Keywords: Alanine-glyoxylate aminotransferase 2, Coronary heart disease, Diabetes mellitus, Asymmetric dimethylarginine, rs37369 polymorphism

JOURNAL OPEN ACCESS

2014 Volume 21 Issue 10 Pages 1022-1030

DOI https://doi.org/10.5551/jat.23077

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Abstract

Aim: 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).
Conclusion: 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.

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