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磷脂酶A2G7基因中的非同义多态性与中国南方人群冠心病风险相关。

Nonsynonymous polymorphisms in PLA2G7 gene are associated with the risk of coronary heart disease in a southern Chinese population.

作者信息

Hong Mei, Zhang Mengyao, Lu Xiang

机构信息

The Second Clinical Medical School of Nanjing Medical University, Nanjing, China.

出版信息

Mamm Genome. 2015 Apr;26(3-4):191-9. doi: 10.1007/s00335-015-9559-x. Epub 2015 Feb 18.

Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays an important role in coronary heart disease (CHD). This study was aimed to investigate the associations of polymorphisms (R92H, V279F, I198T, and A379V) in PLA2G7 with CHD. A total of 322 patients with CHD and 414 CHD-free controls were included in the study. Polymorphisms in PLA2G7 were sequenced by DNA Sequencer and statistical analyses were performed to study the associations between polymorphisms and CHD. RH + HH genotype, RH genotype, and H allele of R92H were significantly associated with an increased risk of CHD (P = 0.005, P = 0.009, and P = 0.003, respectively), while no associations were observed between V279F and I198T and CHD (A379V was not analyzed because of deviation from Hardy-Weinberg equilibrium). Correlations between R92H and CHD still existed after adjustment for confounding risk factors of CHD (P = 0.001). Furthermore, stratified analyses showed subgroups of the senior, hypertension, non-smoking, non-diabetics, and male subjects brought a higher risk for CHD (P = 0.015, P = 0.001, P = 0.001, P = 0.002, and P = 0.004, respectively). We also observed a lower level of protective factor HDL-C in CHD patients carrying genotype RH + HH than patients with RR (P = 0.047). Furthermore, we conducted haplotype analysis and detected more harmful effects of haplotypes HVI and RVT as compared with other haplotypes (P = 2.538 × 10(-3) and P = 0.031). These findings indicated that R92H variant in PLA2G7 gene might contribute to CHD susceptibility in a southern Chinese population.

摘要

脂蛋白相关磷脂酶A2(Lp-PLA2)在冠心病(CHD)中起重要作用。本研究旨在探讨PLA2G7基因多态性(R92H、V279F、I198T和A379V)与冠心病的关联。该研究共纳入322例冠心病患者和414例无冠心病对照者。通过DNA测序仪对PLA2G7基因多态性进行测序,并进行统计分析以研究多态性与冠心病之间的关联。R92H的RH + HH基因型、RH基因型和H等位基因与冠心病风险增加显著相关(P分别为0.005、0.009和0.003),而未观察到V279F和I198T与冠心病之间存在关联(由于偏离哈迪-温伯格平衡,未对A379V进行分析)。在对冠心病的混杂危险因素进行校正后,R92H与冠心病之间的相关性仍然存在(P = 0.001)。此外,分层分析显示,老年、高血压、不吸烟、非糖尿病和男性亚组患冠心病的风险更高(P分别为0.015、0.001、0.001、0.002和0.004)。我们还观察到,携带基因型RH + HH的冠心病患者中保护性因子HDL-C水平低于携带RR基因型的患者(P = 0.047)。此外,我们进行了单倍型分析,发现与其他单倍型相比,单倍型HVI和RVT的有害作用更大(P = 2.538×10(-3)和P = 0.031)。这些发现表明,PLA2G7基因中的R92H变异可能在中国南方人群中导致冠心病易感性。

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