高脂血症患者中对氧磷酶1（PON1）L55M和Q192R基因多态性与冠心病风险：可能关联的临床研究
PON1 L55M and Q192R gene polymorphisms and CAD risks in patients with hyperlipidemia : Clinical study of possible associations.
作者信息
Chen H, Ding S, Zhou M, Wu X, Liu X, Liu J, Wu Y, Liu D
机构信息
Southern Medical University, Guangzhou, China.
Inner Mongolia People's Hospital, Inner Mongolia, China.
出版信息
Herz. 2018 Nov;43(7):642-648. doi: 10.1007/s00059-017-4611-0. Epub 2017 Aug 23.
OBJECTIVE
A decreased plasma high density lipoprotein (HDL) cholesterol level is a strong risk factor for coronary artery disease (CAD). Antioxidant activity of HDL mainly lies in the activity of paraoxonase (PON). This study aimed to investigate the relationships between PON1 L55M and Q192R polymorphisms, and the risks of CAD in patients with hyperlipidemia.
METHODS
From January 2014 to January 2016, 244 patients were divided into hyperlipidemia, hyperlipidemia + CAD, and control groups. The hyperlipidemia and hyperlipidemia + CAD groups were designated as the case group. Serum PON1 concentrations were measured using the enzyme-linked immunosorbent assay. After isolating genomic DNA, the PON1 L55M and Q192R genes were amplified by polymerase chain reaction and sequenced.
RESULTS
In the case group, the genotypes LM and LL were detected significantly more often than in the control group, as were the alleles R (33.33%, 42.12%) and L (22.78%, 29.11%). The frequency of QR and RR genotypes was significantly higher in the hyperlipidemia + CAD group than in the hyperlipidemia group; the allele R in the hyperlipidemia + CAD group (42.77%) was more frequent than in the hyperlipidemia group (23.78%). The Q192R polymorphism was associated with low serum PON1 concentrations, and the lowest concentration was observed in the 192QR + 192RR genotype (P = 0.03). Logistic regression analysis showed a significant correlation between the 192R allele and smoking (P = 0.03), body mass index (P = 0.02), systolic blood pressure (P = 0.004), total cholesterol (P = 0.03), triglycerides (P = 0.01), HDL (P = 0.004), and low density lipoprotein (P = 0.02).
CONCLUSION
The PON1 alleles 192R and 55L are associated with CAD, and the Q192R polymorphism may be a risk factor for CAD.
目的
血浆高密度脂蛋白（HDL）胆固醇水平降低是冠状动脉疾病（CAD）的一个重要危险因素。HDL的抗氧化活性主要在于对氧磷酶（PON）的活性。本研究旨在探讨对氧磷酶1（PON1）L55M和Q192R基因多态性与高脂血症患者CAD风险之间的关系。
方法
2014年1月至2016年1月，将244例患者分为高脂血症组、高脂血症合并CAD组和对照组。高脂血症组和高脂血症合并CAD组被指定为病例组。采用酶联免疫吸附测定法测定血清PON1浓度。分离基因组DNA后，通过聚合酶链反应扩增PON1 L55M和Q192R基因并进行测序。
结果
在病例组中，LM和LL基因型的检测频率显著高于对照组，等位基因R（33.33%，42.12%）和L（22.78%，29.11%）也是如此。高脂血症合并CAD组中QR和RR基因型的频率显著高于高脂血症组；高脂血症合并CAD组中的等位基因R（42.77%）比高脂血症组（23.78%）更常见。Q192R基因多态性与血清PON1浓度降低有关，在192QR + 192RR基因型中观察到最低浓度（P = 0.03）。逻辑回归分析显示192R等位基因与吸烟（P = 0.03）、体重指数（P = 0.02）、收缩压（P = 0.004）、总胆固醇（P = 0.03）、甘油三酯（P = 0.01）、HDL（P = 0.004）和低密度脂蛋白（P = 0.02）之间存在显著相关性。
结论
PON1等位基因192R和55L与CAD相关，Q192R基因多态性可能是CAD的一个危险因素。
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