过氧化物酶体增殖物激活受体多态性及基因-基因交互作用对脉压的影响  

Association and effects of gene-gene interactions between peroxisome proliferator-activated receptor and pulse pressure

作　　者：周慧 丁一 武鸣[2] 范伟 俞浩[2] 周正元[4] 顾淑君[4] 张丽君[3] 董晨[3] 郭志荣 

机构地区：[1]苏州市工业园区疾病防治中心,215021 [2]江苏省疾病预防控制中心慢病所,南京210009 [3]苏州大学医学部公共卫生学院流行病与卫生统计教研室,215123 [4]江苏省常熟市疾病预防控制中心慢病科,215500

出　　处：《中华流行病学杂志》2017年第10期1404-1409,共6页Chinese Journal of Epidemiology

基　　金：国家自然科学基金（81502869）;苏州市“科教兴卫”青年科技项目（KJXW2014060,KJXW2015063）

摘　　要：目的探讨过氧化物酶体增殖物激活受体（PPAR）单核苷酸多态性（SNP）以及基因-基因交互作用对脉压差的影响。方法基于江苏省代谢综合征和多代谢异常综合防治研究（PMMJS）队列，采用单纯随机抽样方法随机抽取其中研究对象820例，选取3个PPARα、2个PPAR8和5个PPARy的SNP位点并进行检测，运用广义多因子降维法（GMDR）模型检测10个SNP的基因-基因交互作用与高血压的关联。结果PPAR7的rs1805192的突变基因型（PA＋AA）携带者与野生型（PP）相比，脉压差水平显著变化（1．341mmHg，95％CI：0．431～2．252mmHg）。GMDR模型分析显示，在脉压差≥30mmHg的亚组中，PPARα基因的rs135539、PPARδ的rs2016520、PPARγ的rs10865710、rs1805192、rs709158、rs3856806组成的六阶模型平均检验准确度为0．577，交叉验证一致性为10／10，为最优模型。而在脉压差≤40mmHg的亚组中，二阶交互作用模型与脉压差显著相关，平均检验准确度为0．628，交叉验证一致性为10／10。结论PPARγ的rs1805192多态性与脉压差水平有关联，PPARa基因的rs135539、PPAR8的rs2016520和PPARγ的rs10865710、rs1805192、rs709158、rs3856806六个SNP间基因-基因交互作用与脉压差间具有显著性关联。Objective To investigate the association between ten single nucleotide polymorphisms （SNPs） in the peroxisome proliferator-activated receptors and pulse pressure （PP） as well as the relationships between gene-gene interaction between PPARα/δ/γ genes and PP. Methods A total of 820 subjects, with 550 females and 270 males, were recruited from a cohort study of ＂Prevention of Metabolic Syndrome and Multi-metabolic Disorders in Jiangsu Province of China Study （PMMJS）＂. Ten SNPs of PPARα/δ/γ genes were selected. GMDR software （version 1.0.1） was used to evaluate the gene-gene interactions among PPARs SNPs associated with PP. Results The mean levels of PP in people with mutant genotype ofrslS05192 in PPAR7 genes （PA＋AA） showed asignificant increase by 1.341 mmHg （95%CI： 0.431-2.252 mmHg） when compared to the persons with wild genotype （PP）. In the subgroup of subjects with more than 30 mmHg levels of PP, a six-locus model comprised rs135539 of PPARα, rs2016520 of PPARδ, rs10865710, rs1805192, rs709158 and rs3856806 of PPARγshowed a highest level of prediction accuracy （0.577） and displayed a better cross-validation consistency （10/10）. In the subgroup of subjects with less than 40 mmHg levels of PP, a two-locus model was statistically associated with PP with 0.628 of prediction accuracy and 10/10 of cross-validation consistency. Conclnsion PPARy rs1805192 was associated with the occurrence of PP. Gene-gene interactions among rs135539 of PPARa, rs2016520 of PPARS, rs10865710, rs1805192, rs709158 and rs3856806 of PPARγ were all significantly related to PP.

关 键 词：脉压差 过氧化物酶体增殖物激活受体 广义多因子降维法 交互作用 

分 类 号：R181.3[医药卫生—流行病学]