Wang Xue-Bin, Cui Ning-Hua, Zhang Shuai, Guo Shu-Ren, Liu Ze-Jin, Ming Liang
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Clinical Laboratory, Children's Hospital of Zhengzhou, Zhengzhou, China.
Front Physiol. 2017 Nov 14;8:916. doi: 10.3389/fphys.2017.00916. eCollection 2017.
Inhibition of poly(ADP-ribose) polymerase (PARP) may protect against coronary artery disease (CAD) in animal models, and rs1136410, a non-synonymous single nucleotide polymorphism (SNP) in , has a potential impact on PARP activities . This two-stage case-control study, involving 2803 CAD patients and 2840 controls, aimed to investigate the associations of rs1136410 with CAD development, lipid levels, PARP activities, 8-hydroxy-2'-dexyguanosine (8-OHdG), and interleukin (IL)-6 levels in a Chinese Han population. Assuming a recessive model, the variant genotype GG of SNP rs1136410 showed a significantly inverse association with CAD risk (adjusted odds ratio (OR) = 0.73, < 0.001), left main coronary artery (LMCA) lesions ( = 0.003), vessel scores ( = 0.003), and modified Gensini scores ( < 0.001). There were significant correlations of SNP rs1136410 with higher levels of total cholesterol (TC) and lower levels of high-density lipoprotein cholesterol (HDL-c). In gene-environment interaction analyses, participants with the variant genotype GG, but without smoking habit, type 2 diabetes mellitus, and hyperlipidemia, conferred an 84% ( < 0.001) decreased risk of CAD. The genotype-phenotype correlation analyses further supported the functional roles of SNP rs1136410 in decreasing PARP activities and 8-OHdG levels. Taken together, our data suggest that SNP rs1136410 may confer protection against CAD through modulation of PARP activities and gene-environment interactions in a Chinese Han population.
在动物模型中,抑制聚(ADP - 核糖)聚合酶(PARP)可能对冠状动脉疾病(CAD)具有保护作用,而rs1136410是位于 中的一个非同义单核苷酸多态性(SNP),对PARP活性有潜在影响。这项两阶段病例对照研究纳入了2803例CAD患者和2840例对照,旨在探讨rs1136410与中国汉族人群CAD发生、血脂水平、PARP活性、8 - 羟基 - 2'-脱氧鸟苷(8 - OHdG)及白细胞介素(IL)-6水平之间的关联。假设为隐性模型,SNP rs1136410的变异基因型GG与CAD风险(校正比值比(OR) = 0.73,< 0.001)、左主干冠状动脉(LMCA)病变( = 0.003)、血管评分( = 0.003)及改良Gensini评分(< 0.001)呈显著负相关。SNP rs1136410与较高的总胆固醇(TC)水平和较低的高密度脂蛋白胆固醇(HDL - c)水平存在显著相关性。在基因 - 环境相互作用分析中,具有变异基因型GG但无吸烟习惯、2型糖尿病和高脂血症的参与者,CAD风险降低了84%(< 0.001)。基因型 - 表型相关性分析进一步支持了SNP rs1136410在降低PARP活性和8 - OHdG水平方面的功能作用。综上所述,我们的数据表明,SNP rs1136410可能通过调节PARP活性和基因 - 环境相互作用,对中国汉族人群的CAD起到保护作用。