PPAR单核苷酸多态性基因-基因交互作用与载脂蛋白AⅠ/载脂蛋白B100比值的关系

Association between peroxisome proliferator-activated receptor and gene-gene interactions with the apolipoprotein A Ⅰ/apolipoprotein B100 ratio

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）与载脂蛋白AⅠ（ApoAⅠ）/载脂蛋白B100（ApoB100）比值水平的关联以及多个SNP的交互作用对ApoA Ⅰ/ApoB100比值水平的影响.方法 对630名研究对象进行PPAR 10个SNP多态性检测.运用线性回归模型分析10个SNP与ApoA Ⅰ/ApoB100比值水平的关联,采用广义多因子降维法（GMDR）模型分析10个SNP的基因-基因交互作用.结果 在调整性别、年龄、吸烟、饮酒、高脂饮食、低纤维饮食和职业体力活动后,与野生型基因携带人群相比,rs 1800206位点（LV＋VV）基因型携带者以及rs3856806位点（CT ＋TT）基因型携带者的ApoA Ⅰ/ApoB100比值水平均较低,差异值（95％ CI）分别为-1.19（-1.88～-0.50）和-0.77（-1.40～-0.14）;rs4253778位点（GC＋ CC）基因型携带者的ApoA Ⅰ/ApoB100比值水平较高,差异值（95％ CI）为0.80（0.08 ～ 1.52）.GMDR模型发现二、三、四、五、六和八阶交互作用模型差异有统计学意义（P＜0.05）,其中八阶模型（包括PPARα的rs4253778、rs1800206,PPARβ的rs2016520、rs9794,PPARγ的rs10865710、rs3856806、rs709158和rs1805192）交叉验证一致性为7/10,平均检验准确度为0.624,为最佳模型（P=0.01）.结论 PPARα的rs1800206及PPARγ的rs3856806与ApoA Ⅰ/ApoB100比值水平降低有关联;PPARα的rs4253778与ApoA Ⅰ/ApoB100比值水平升高有关联.PPARα的rs4253778、rs 1800206和PPARβ的rs2016520、rs9794和PPARγ的rs10865710、rs3856806、rs709158和rs 1805192等8个SNP之间的交互作用对ApoA Ⅰ/ApoB100比值水平有显著影响.

Objective To investigate the association between ten single nucleotide polymorphisms （SNPs） in the peroxisome proliferator-activated receptors （PPARot,3,γ） with apolipoprotein A Ⅰ/apolipoprotein B100 （ApoA Ⅰ/ApoB100） ratio and the additional role of a gene-gene interactions among the 10 SNPs.Methods Participants were recruited under the framework of the Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province （PMMJS） cohort population survey in the urban community of Jiangsu province of China.A total of 630 subjects were randomly selected and no individual was related.Ten SNPs （rs135539,rs4253778,rs1800206,rs2016520,rs9794,rs10865710,rs1805192,rs709158,rs3856806 and rs4684847） were selected from the HapMap database,which covered PPARα,PPARβ and PPARγ.A linear regression model was used to analyze the relations between ten SNPs in the PPARs and ApoA Ⅰ/ApoB100 ratio level.Mean difference and 95% CI were calculated.Interactions were explored by using the method of Generalized Multifactor Dimensionality Reduction （GMDR）.Results After adjusting for age,gender,smoking status,alcohol consumption,occupational physical activity,high-fat diet as well as low-fiber diet,both rs1800206 and rs3856806 were significantly associated with a decreased level of ApoA Ⅰ/ApoB100 ratio,mean difference （95%CI） values were-1.19（-1.88 to-0.50） and-0.77 （-1.40 to-0.14）.Whereas rs4253778 was significantly associated with an increased level of ApoA Ⅰ /ApoB100 ratio,Mean difference （95% CI） values was 0.80 （0.08 to 1.52）.GMDR analysis showed a significant gene-gene interaction among rs4253778,rs1800206 of PPARo,rs9794,rs2016520 of PPARβ and rs10865710,rs3856806,rs709158,rs1805192 of PPARγ for eight-dimension models （P =0.01）,in which prediction accuracy was 0.624 and cross-validation consistency was 7/10.Conclusions The rs1800206 of PPARo and rs3856806 of PPARγ are significantly associated with a decreased level of ApoA Ⅰ/ApoB100 ratio while rs4253778 of PPARα is associated with an increased level of ApoA Ⅰ/ApoBl00 ratio.There is a gene-gene interaction between multiple SNPs.