Association of the AGXT2 V140I polymorphism with risk for coronary heart disease in a Chinese population.
Association of the AGXT2 V140I polymorphism with risk for coronary heart disease in a Chinese population.
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DOI：
10.5551/jat.23077
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发表时间：
2014-10
影响因子：
4.4
通讯作者：
Ji-Peng Zhou;Yongping Bai;Xiaolei Hu;Da-Bin Kuang;Rui-zheng Shi;Y. Xiong;Wei Zhang;J. Xia;Bi-Lian Chen;Tian-lun Yang;Xiaoping Chen
中科院分区：
文献类型：
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作者：
Ji-Peng Zhou;Yongping Bai;Xiaolei Hu;Da-Bin Kuang;Rui-zheng Shi;Y. Xiong;Wei Zhang;J. Xia;Bi-Lian Chen;Tian-lun Yang;Xiaoping Chen
目的不对称二甲基精氨酸（ADMA）是一氧化氮合酶（NOS）抑制剂，可减少NO的产生，促进心血管疾病的发生发展。丙氨酸乙醛酸转氨酶2（AGXT 2）在ADMA代谢中起重要作用。本研究旨在探讨AGXT 2 V140 I（rs37369 G>A）多态性与中国人群冠心病（CHD）的关系。方法采用病例对照研究方法，对1103例正常人和942例冠心病患者进行研究。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对患者进行rs37369基因分型。采用酶联免疫吸附试验（ELISA）测定健康对照者血浆ADMA浓度。结果冠心病组rs37369 GG基因型频率显著高于对照组（18.5%对14.8%，p=0.025），与吸烟者冠心病风险增加显著相关（OR=2.21，95% CI：1.24-3.92，p=0.007），糖尿病患者CHD风险略有增加（OR=1.92; 95% CI：0.94-3.91，p=0.074）。rs37369与冠心病风险的相关性在吸烟合并糖尿病的人群中进一步增加（OR=3.32，95%CI：1.14-9.67，p=0.028）。吸烟和rs37369 GG纯合子患者的血浆ADMA水平显著高于rs37369 A等位基因携带者（p=0.004）。然而，在非吸烟者中，rs37369 GG纯合子患者的血浆ADMA浓度显著低于rs37369 A等位基因携带者（p=0.003）。此外，rs37369 GG纯合子吸烟者的血浆ADMA浓度显著高于具有相同基因型的非吸烟者（p=0.012）。结论AGXT 2基因rs37369多态性与吸烟者和糖尿病患者冠心病的发病风险相关。这种增加的风险可能是由于血浆ADMA水平增加。
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.