Study Of Genetic Polymorphism Of Peroxisome Proliferator-activated Receptors And Haplotype On Body Mass Index And Waist Circumference

Objective1. To explore the association between SNPs (single nucleotide polymorphism,SNP) of peroxisome proliferator-activated receptors (PPARs) and BMI (body massindex) and waist circumference (WC)2. To discuss the gene-gene interaction of SNPs in PPARs subtypes and the effecton BMI and WC.3. Haplotype ananlysis on the association between SNPs in PPARs and BMI andWCMethods1. Participants were recruited within the framework of the PMMJS cohortpopulations survey in the urban community of Jiangsu province of China.820subjects(270males,550females) were randomly selected and no individuals were related.There are513non-obese subjects and307obese subjects,416non-abdominal obesesubjects and404abdominal obese subjects. Ten SNPs (rs135539, rs4253778,rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806,rs4684847) were genotyped and analyzed. Two approaches were employed toananlysis frequent and minor alleles for ten SNPs (rs135539, rs4253778, rs1800206,rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, rs4684847).rs4253778was detected by plymerase chain reaction restriction fragment lengthpolymorphisms (PCR-RFLP), and the left nine SNPs was detected by Taqmanfluorescence probe. 2. The logistic regression model was used to examine the association betweenPPARs polymorphisms and BMI and WC, odds ratio (OR) and95%confident interval(95%CI) were calculated. Odds were adjusted for the potential confounding effects ofgender, age, smoke, alcohol, high fat diet, low fiber diet and occupational activity.3. Generalized MDR (GMDR) was employed to analysis the interaction among10SNPs, some parameters was calculated, including cross-validation consistency, thetesting balanced accuracy, and the sign test, to assess each selected interaction.4. The analysis of deviation from Hardy–Weinberg equilibrium, estimation oflinkage disequilibrium (LD) between polymorphisms, association of haplotypes withBMI and WC were performed using SNPStats.Results1. Logistic regression analysis showed that the association between genotypes ofvariants in rs2016520and decreased obesity risk, after adjustment for gender, age,smoke status, alcohol consumption, occupational activity, high fat and low fiber dietstyle, the carriers of C allele of the rs2016520polymorphism revealed an decreasedobesity risk than those with TT variants (CC+CT versus TT, adjusted OR=0.63,95%CI=0.47–0.84, p=0.002), the carriers of C allele of the rs2016520polymorphism alsorevealed an decreased abdominal obesity risk than those with TT variants (CC+CTversus TT, adjusted OR=0.68,95%CI=0.52–0.90, p=0.005). However, the othereight SNPs in PPARs did not exhibit any significant association with obesity andabdominal obesity before or after covariates adjustment.2. The results obtained from GMDR analysis indicated a significant two-locusmodel (p=0.0010) involving rs2016520and rs10865170, and a significant three-locusmodel (p=0.0010) involving rs2016520, rs9794and rs10865170, indicating a potentialgene–gene interaction between rs2016520and rs10865170and among rs2016520,rs9794and rs10865170on BMI. A significant three-locus model (p=0.0010) involvingrs2016520, rs10865170and rs1805192, and a significant five-locus model (p=0.0010)involving rs135539, rs2016520, rs10865710, rs1805192and rs709158, indicating a potential gene–gene interaction among rs2016520, rs10865170and rs1805192, andamong rs135539, rs2016520, rs10865710, rs1805192and rs709158on WC.3. Results of haplotype ananlysis indicated that C-C haplotype in PPARδrs2016520and rs9794was associated with lower obesity and abdominal obesity risk,OR(95%CI) were0.64(0.48-0.84) and0.61(0.47-0.79) repectively. G-Pro-T haplotypein PPARγ rs10865710, rs1805192and rs709158was associated with higher abdominalobesity risk, OR(95%CI) was2.05(1.15-3.99).Conclusions1. rs2016520in PPARδ was associated with both obesity and abdominal obesity,we did not found the association of other nine SNPs and obesity or abdominal obesity.2. A significant interaction on BMI was obtained between rs2016520andrs10865170, among rs2016520, rs9794and rs10865170, we also found a significantinteraction among rs2016520, rs10865170and rs1805192, and among rs135539,rs2016520, rs10865710, rs1805192and rs709158on WC.3. C-C haplotype in PPARδ rs2016520and rs9794was associated with lowerobesity and abdominal obesity risk, and G-Pro-T haplotype in PPARγ rs10865710,rs1805192and rs709158was associated with higher abdominal obesity risk. C-Chaplotype in PPARδ rs2016520and rs9794may be genetics marker of obesity andabdominal obesity, and G-Pro-T haplotype in PPARγ rs10865710, rs1805192andrs709158may be genetics marker of abdominal obesity.