PPARγ基因多态性与脂蛋白(a)水平的单倍型分析

Haplotype Analysis of PPARγ Gene Polymorphisms and the Lipoprotein (a) Level.

作者信息

Shen Chao, Fan Wei, Xie Hui-Jian, Wu Ming, Zhou Zheng-Yuan, Guo Zhi-Rong, Dong Chen

机构信息

Dept. of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.

The Center for Disease Control and Prevention of Suzhou Industry Park, SuZhou, China.

出版信息

Iran J Public Health. 2018 Jul;47(7):973-979.

PMID:30181995

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6119570/

Abstract

BACKGROUND

Lipoprotein (a) [Lp(a)], as an independent risk factor for cardiovascular disease, is more likely to be genetically determined according to the increasing evidence of epidemiologic and clinical studies in recent years. Peroxisome proliferator-activated receptor (PPAR) γ, the ligand-activated transcription factors, was considered as an indispensable role in the process of lipid metabolism. This study was designed to explore the associations of three single-nucleotide polymorphisms (SNPs) and the haplotypes of the peroxisome proliferator-activated receptor (PPAR)γ gene with the level of Lp(a).

METHODS

Participants were recruited under the framework of the PMMJS (The Prevention of Metabolic Syndrome (MS) and Multi-metabolic Disorders in Jiangsu Province of China Study) from Apr 1999 to Jun 2004. Overall, 644 subjects were randomly selected and 3 SNPs of PPARγ gene (rs10865710, rs1805192, rs4684847) were genotyped.

RESULTS

After adjusting for age, sex, cigarette smoking, alcohol drinking, waist circumference and body mass index, rs4684847 was significantly associated with Lp (a). The presence of the rs4684847 T allele (CT+TT) have a lower level of Lp (a) than the allele (CC) in the dominant model, mean difference was -27.30 (95% : -52.88∼-1.73) mg/L, <0.05. G-P-T and G-A-T haplotype were associated with lower levels of Lp (a) (=0.0041 and <0.0001), mean difference was 49.79 (95% -97.52∼-2.06) mg/L and 17.75 (95% : -25.75∼-9.75) mg/L.

CONCLUSION

PPAR gamma polymorphisms (rs10865710, rs1805192, rs4684847) and haplotypes may be the genetic risk factors for Lp (a) level.

摘要

背景

近年来，流行病学和临床研究证据不断增加，脂蛋白(a)[Lp(a)]作为心血管疾病的独立危险因素，更有可能由基因决定。过氧化物酶体增殖物激活受体(PPAR)γ是一种配体激活的转录因子，被认为在脂质代谢过程中起着不可或缺的作用。本研究旨在探讨过氧化物酶体增殖物激活受体(PPAR)γ基因的三个单核苷酸多态性(SNP)和单倍型与Lp(a)水平的相关性。

方法

在1999年4月至2004年6月的PMMJS（中国江苏省代谢综合征(MS)和多代谢紊乱预防研究）框架下招募参与者。总共随机选择了644名受试者，并对PPARγ基因的3个SNP(rs10865710、rs1805192、rs4684847)进行基因分型。

结果

在调整年龄、性别、吸烟、饮酒、腰围和体重指数后，rs4684847与Lp(a)显著相关。在显性模型中，rs4684847 T等位基因(CT+TT)的Lp(a)水平低于等位基因(CC)，平均差异为-27.30(95%：-52.88∼-1.73)mg/L，P<0.05。G-P-T和G-A-T单倍型与较低的Lp(a)水平相关(P=0.0041和P<0.0001)，平均差异分别为49.79(95%：-97.52∼-2.06)mg/L和17.75(95%：-25.75∼-9.75)mg/L。