过氧化物酶体增殖物激活受体以及基因一基因交互作用与脂质蓄积指数水平的关系

海波; 解惠坚; 郭志荣; 武鸣; 陈秋; 周正元; 俞浩; 丁一

Abstract

海波,解惠坚,郭志荣,武鸣,陈秋,周正元,俞浩,丁一.过氧化物酶体增殖物激活受体以及基因一基因交互作用与脂质蓄积指数水平的关系[J].Chinese journal of Epidemiology,2013,34(11):1071-1076

过氧化物酶体增殖物激活受体以及基因一基因交互作用与脂质蓄积指数水平的关系

Association of both peroxisome proliferator-activated receptor,gene-gene interactions and thelipid accumulation product

Received:June 13, 2013

DOI：10.3760/cma.j.issn.0254-6450.2013.011.006

KeyWord: 脂质蓄积指数过氧化物酶体增殖物激活受体多态性交互作用

English Key Word: Lipid accumulation product Peroxisome proliferator-activated receptors Polymorphism Interaction

FundProject:卫生部科学研究基金资助项目(WKJ2004—2—014)

Author Name	Affiliation	E-mail
HAl B0	Department of Public Health,Soochow University,Suzhou 215123,China
XlE Hui-jian	Department of Public Health,Soochow University,Suzhou 215123,China
GUO Zhi-rong	Department of Public Health,Soochow University,Suzhou 215123,China	guozhirong28@163.com
WU Ming	Jiangsu Provincial Center for Disease Controf and Prevention
CHEN Qiu	Department of Radiation Medicinc and Protection,Soochow University,Suzhou
ZHOU Zheng-yuan	Changshu Center for Disease Control and Prevention,Jiangsu Province
YU Hao	Jiangsu Provincial Center for Disease Controf and Prevention
丁一	Department of Public Health,Soochow University,Suzhou 215123,China

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Abstract:

目的探讨过氧化物酶体增殖物激活受体(PPAR)lo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lO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的基因一基因交互作用。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，rsl800206位点(Lv+vv)基因型携带者，rsl805192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)为一14.67(-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PPARa的rsl35539、rsl800206，PPAR 6的rs2016520及PPAR丫的rsl0865710、rs3856806、rs709158、rsl805192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PPARa的rsl800206及PPAR吖的rsl805192和rs3856806与LAP水平的升高有关；PPAR8的rs2016520与LAP水平的降低有关。PPARct的rsl35539、rsl800206，PPAR8的rs2016520及PPAR7的rsl0865710、rs3856806、rs709158、rsl805192、rs4684847八个SNP之间的交互作用对LAP水平具有显著影响。

English Abstract:

0bjective To investigate the association of ten single nucleotide polymorphisms(SNPS)in the peroxisome proliferator-activated receptors(PPAR a,6,Y)wi也lipid accumulationproduct(LAP)and the additional role of a gene.gene interactions among the 1 0 SNPs.Methods Participants were recruited under the framework of the PMMJS(Prevention of Multiple MetabolicDisorders and Metabolic Syndrome in Jiangsu province)cohort populations survey in the urbancommunity of Jiangsu province of China.A total of 820 subjects were randomly selected and noindividual was related.Ten SNPs(rsl35539,rs4253778,rsl800206,rs2016520,rs9794,rsl0865710,rsl805192,rs709158,rs3856806 and rs4684847)were selected from the HapMap database,whichcovered PPAR a,PPAR 6 and PPAR Y.A linear regression model was used to analyze the relationsbetween ten SNPS in the PPARs and LAP Mean difference(Difference)and 95%confident interval(95%CI)were calculated.Interactions were explored by using the method of Generalized MultifactorDimensionality Reduction(GMDR).Results After adjusting the factors as age.gender,smokingstatus,occupational physical activity,educationallevel,high.fat diet as well as low.fiber diet,bothrsl800206.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 ofLAP.Difference(95%CI)values was-14.67(-22.97-6.55).GMDR analysis showed a significant gene.gene interactionamong rsl35539,rsl800206 ofPPARa。rs2016520 ofPPAR6 and rsl0865710.rs3856806,rs709158.rsl805192,rs4684847 ofPPARyfor eight-dimensionmodels(P<0.05),inwhichprediction accuracywas 0.5902 and cross-validation consistency was 10/10.Conclusion The rsl800206 of PPAR a andrsl805192,rs3856806 of PPAR Y were significantly associated with the increased level of LAP；rs20 l6520 of PPAR 6 was associated with the decreased level of LAE There was a gene-geneinteraction between multiple SNPs.

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