过氧化物酶体增殖物激活受体以及基因——基因交互作用与脂质蓄积指数水平的关系

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)与脂质蓄积指数(LAP)水平的关联,以及多个SNP的交互作用对LAP水平的影响.方法 检测820名研究对象的PPAR 10个SNP多态性.运用线性回归模型分析10个SNP与LAP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、低纤饮食、文化程度和职业体力活动后,与野生型基因携带人群相比,rs1800206位点(LV+VV)基因型携带者,rs1805192位点(PA+AA)基因型携带者以及rs3856806位点(CT+TT)基因型携带者的LAP水平均显著升高,差异值(95％CI)分别为32.47(22.62 ～42.31)、12.97(4.61 ～ 21.33)和12.49(4.24 ～ 20.75);而rs2016520位点(TC+CC)基因型携带者的LAP水平显著降低,差异值(95％CI)为-14.67(-22.97 ～-6.55).GMDR模型发现二阶、三阶、四阶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rs135539、rs1800206,PPAR δ的rs2016520及PPARγ的rs10865710、rs3856806、rs709158、rs1805192和rs4684847)交叉验证一致性为10/10,平均检验准确度为0.5902,为最佳模型.结论 PPARα的rs1800206及PPARγ的rs1805192和rs3856806与LAP水平的升高有关；PPARδ的rs2016520与LAP水平的降低有关.PPARα的rs135539、rs1800206,PPARδ的rs2016520及PPARγ的rs10865710、rs3856806、rs709158、rs1805192、rs4684847八个SNP之间的交互作用对LAP水平具有显著影响.%Objective To investigate the association of ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (PPARα,δ,γ) with lipid accumulation product (LAP) 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 Metabolic Syndrome in Jiangsu province) cohort populations survey in the urban community of Jiangsu province of China.A total of 820 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,PPARδ and PPARγ.A linear regression model was used to analyze the relations between ten SNPs in the PPARs and LAE Mean difference (Difference) 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,gender,smoking status,occupational physical activity,educational level,high-fat diet as well as low-fiber diet,both rs1800206,s1805192 and rs3856806 were significantly associated with the increased level of LAP.Difference (95％ CI) values were 32.47 (22.62-42.31),12.97 (4.61-21.33) and 12.49 (4.24-20.75).Whereas rs2016520 was significantly associated with the decreased level of LAP.Difference (95％CI)values was-14.67 (-22.97--6.55).GMDR analysis showed a significant gene-gene interaction among rs135539,rs1800206 of PPARα,rs2016520 of PPARδ and rs10865710,rs3856806,rs709158,rs 1805192,rs4684847 of PPARγfor eight-dimension models (P＜ 0.05),in which prediction accuracy was 0.5902 and cross-validation consistency was 10/10.Conclusion The rs1800206 of PPAR α and rs1805192,rs3856806 of PPARγ were significantly associated with the increased level of LAP;rs2016520 of PPAR δ was associated with the decreased level of LAE There was a gene-gene interaction between multiple SNPs.