PPARα单核苷酸多态性与低高密度脂蛋白胆固醇血症的关联及与PPARγ的交互作用  

Association and interaction of peroxisome proliferator-activated receptor a with low high- density lipoprotein hyperlipidemia and with peroxisome proliferator-activated receptor γ

作　　者：刘萌萌[1] 顾淑君[1] 郭志荣[1] 武鸣[2] 陈秋[3] 周正元[4] 俞浩[2] 丁一[1] 骆文书[1] 

机构地区：[1]苏州大学医学部公共卫生学院流行病与卫生统计学教研室,215123 [2]江苏省疾病预防控制中心慢病科 [3]苏州大学医学部放射生物学教研室 [4]江苏省常熟市疾病预防控制中心慢病科

出　　处：《中华流行病学杂志》2012年第12期1218-1223,共6页Chinese Journal of Epidemiology

基　　金：卫生部科学研究基金（WKJ2004-2-014）

摘　　要：目的探讨过氧化物酶体增殖物激活受体（PPAR）10个单核苷酸多态性（SNP）以及多个SNP间交互作用与低高密度脂蛋白胆固醇（HDL-C）血症的关联。方法对820名研究对象进行PPAR10个SNP多态性检测，以随访时测得的HDL-C值判定低HDL-C血症。运用logistic回归模型分析10个SNP与低HDL-C血症的关联，GMDR模型分析10个SNP的基因-基因交互作用。结果调整性别、年龄、吸烟、体力活动、高脂饮食和低纤饮食后，与野生型基因携带人群相比，rsl35539突变等位基因携带人群（AC＋CC）发生低HDL-C血症的OR=1．46（95％CI：1．07～1．99），rsl800206突变等位基因携带人群（Lv＋vv）发生低HDL—C血症的OR=O．62（95％C／：0．42～0．90）。GMDR模型结果显示，PPARa的rsl35539、rs4253778及PPAR7的rsl0865710、rs3856806、rs709158和rs4684847在SNP间的交互作用有统计学意义（P=0．0107）。结论PPARa的rsl35539多态性与低HDL．C血症有关联，与PPARa的rs4253778和PPAR7的~10865710、rs3856806、rs709158和rs4684847间存在交互作用。Objective To investigate the association of ten single nucleotide polymorphisms （SNPs） in the peroxisome proliferator-activated receptors （α, β, γ） with low high-density lipoprotein- cholesterol （HDL-C） hyperlipidemia and the additional role of a gene-gene interactions among the 10 SNPs. Methods Participants were recruited under the framework of the PMMJS （Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province） cohort populations survey, in the urban community of Jiangsu province, China. 820 subjects （579 normal HDL-C, 241 low HDL-C） were randomly selected, with one of them related to each other. Ten SNPs （rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, rs4684847） were selected from the HapMap database, which covered PPARct, PPAR8 and PPAR7. Logistic regression model was used to examine the association between ten SNPs in the PPARs and low HDL-C. Odds ratios （OR） and 95% confident interval （95%CI） were calculated. Interactions were explored by using the method of Generalized Multifactor Dimensionality Reduction （GMDR）. Results After adjusting the factors as age, sex, smoking status, occupational physical activity, high-fat diet as well as low-fiber diet, both rs135539 and rs1800206 were significantly associated with the incidence of low HDL-C, with the OR （95%CI） values as 1.46（1.07-1.99） and 0.62（0.42-0.90）. No statistically significantdifference was found between other SNPs and the occurrence of low HDL-C. Data from GMDR analysis showed significant gene-gene interaction among rs135539, rs4253778 of PPAR a and rs10865710, rs3856806, rs709158 and rs4684847 of PPAR7 （P=0.0107）. Conclusion PPAR ct rs135539 was associated with the occurrence of low HDL-C, and had interacted with rs4253778, rs10865710,rs3856806,rs709158 and rs4684847.

关 键 词：低高密度脂蛋白胆固醇血症 过氧化物酶体增殖物激活受体 多态性 交互作用 

分 类 号：R589.2[医药卫生—内分泌]