Interactions Of Haplotypes In Peroxisome Proliferator-activated Receptor α/γ And Body Mass Index On Triglycerides And High-density Lipoprotein Cholesterol

Objective1. To explore the association between SNPs (single nucleotide polymorphism, SNP)of peroxisome proliferator-activated receptor/γ (PPAR/γ) and TG (triglyceride) andHDL-C (high-density lipoprotein cholesterol).2. Haplotype ananlysis on the association between SNPs in PPAR/γ and TG andHDL-C.3. To investigate the interaction of PPAR/γ haplotypes and BMI on the affects ofTG and HDL-C levels.Methods1. Participants were recruited within the framework of the PMMJS cohortpopulation survey in the urban community of Jiangsu province of China.820subjects(270males,550females) were randomly selected and no individuals were related.There are474normal TG subjects and346high TG subjects,579normal HDL-Csubjects and241low HDL-C subjects. Eight SNPs (rs135539, rs4253778, rs1800206,rs10865710, rs1805192, rs709158, rs3856806, rs4684847) were genotyped andanalyzed. Two approaches were employed to ananlysis frequent and minor alleles foreight SNPs (rs135539, rs4253778, rs1800206, rs10865710, rs1805192, rs709158,rs3856806, rs4684847). Rs4253778was detected by plymerase chain reactionrestriction fragment length polymorphisms (PCR-RFLP), and the left seven SNPs weredetected by Taqman fluorescence probe.2. The logistic regression model was used to examine the association betweenPPAR/γ polymorphisms and TG and HDL-C, odds ratio (OR) and95%confidentinterval (95%CI) were calculated. Odds were adjusted for the potential confounding effects of gender, age, smoke, alcohol, occupational activity，high fat diet and low fiberdiet and.3. SNPStats was used to explore the haplotype association analysis and gene-environment interaction analysis.Results1. All of the PPAR/γ polymorphisms examined were in Hardy-Weinbergequilibrium(P＞0.05) in the whole population. Linkage disequilibrium analysisshowed that there was no significant linkage disequilibrium between thesepolymorphisms(D’＜0.75).2. After adjustment for gender, age, smok status, alcohol consumption,occupational activity, high fat and low fiber diet style, the carriers of C allele of thers135539polymorphism revealed an increased low HDL-C risk than those with AAvariants (AC+CC versus AA, adjusted OR=1.46,95%CI=1.07-1.99), the carriers ofV allele of the rs2016520polymorphism revealed an decreased low HDL-C risk thanthose with LL variants (LV+VV versus LL, adjusted OR=0.62,95%CI=0.42-0.90).After adjustment for gender, age, smoke status, alcohol consumption, occupationalactivity, high fat and low fiber diet style, the carriers of V allele of the rs1800206polymorphism revealed an increased levels of TG than those with LL variants (LV+VVversus LL, adjusted OR=3.88,95%CI=2.69–5.60, p＜0.05), the carriers of T allele ofthe rs3856806polymorphism revealed an increased levels of TG than those with CCvariants (CT+TT versus CC, adjusted OR=1.40,95%CI=1.03–1.90, p＜0.05), thecarriers of A allele of the rs1805192polymorphism revealed an increased levels of TGthan those with CC variants (PA+AA versus PP, adjusted OR=2.56,95%CI=1.88–3.49, p＜0.05). However, the other SNPs in PPAR/γ did not exhibit anysignificant association with TG andHDL-C before or after covariates adjustment.2. Results of haplotype ananlysis indicated that C-L haplotype in PPAR rs135539and rs1800206was associated with lower levels of HDL-C, OR(95%CI) is1.42(1.07-1.89). T-P、C-A and T-A haplotype in PPARγ rs3856806and rs180519was associatedwith higher levels of TG, OR(95%CI) were1.74(1.28-2.36),2.62(1.90-3.62) and2.43(1.65-3.58) repectively.3. Haplotype-obesity interaction analysis noted interaction of obesity with C-L in PPAR, OR (95%CI) was3.10(1.95-4.93). Interaction of obesity with T-P,C-A and T-A in PPARγ, OR (95%CI) was5.06(3.00-8.54),4.84(2.83-8.27) and4.44(2.17-9.10) repectively.Conclusions1. Rs1800206in PPAR, rs1805192、rs2016520in PPARγ were associated withTG, rs135539、rs1800206in PPAR was associated with HDL-C.2. C-L haplotype in PPAR rs135539and rs1800206was associated with lowerHDL-C, and T-P、C-A and T-A haplotype in PPARγ rs3856806and rs180519wereassociated with higher levels of TG.3. Significant interaction among C-L haplotype, T-P haplotype, C-A haplotype andT-A haplotypes and BMI were detected, which providing strong evidence ofgene-nvironment interaction.