Study Of Polymorphisms Of Peroxisome Proliferator-activated Receptor α/γ On Triacylglycerol/highdensity Lipoprotein-cholesterol Ratio And Lowdensity Lipoprotein-cholesterol/highdensity Lipoproteincholesterol Ratio

Objective1. To examine the association between SNPs(single nucleotide polymorphisms, SNPs) of peroxisome proliferator-activated receptor α/γ(PPARα/γ) and Triacylglycerol/Highdensity lipoprotein-cholesterol ratio(TG/HDL- C ratio) and Lowdensity lipoprotein-cholesterol/Highdensity lipoprotein-cholesterol ratio(LDL-C/HDL-C ratio).2. To discuss the gene-gene interaction of SNPs in PPARα/γ subtypes and the effect on TG/HDL-C ratio and LDL-C/HDL-C ratio.3. Haplotype ananlysis on the association between SNPs in PPARα/γ and TG/HDL- C ratio and LDL-C/HDL-C ratio.MethodsParticipants were recruited within the framework of the PMMJS cohort population urvey in the urban community of Jiangsu province of China. 820 subjects(270 males, 550 females) were randomly selected and no individuals were related. Eight SNPs were genotyped and analyzed. Two approaches were employed to ananlysis frequent and minor alleles for eight SNPs(rs135539, rs4253778, rs1800206, rs10865710, rs1805192, rs709158, rs3856806, rs4684847). R4253778 was detected by plymerase chain reaction restriction fragment length polymorphisms(PCR-RFLP), and the left seven SNPs were detected by Taqman fluorescence probe. A linear regression model was used to analyze the relations between ten SNPs in the PPARα/γ and TG/HDL- C ratio and LDL-C/HDL-C ratio. Mean difference(Difference) and 95% confident interval(95%CI) were calculated. Interactions were explored by using the method of Generalized Multifactor Dimensionality Reduction(GMDR). The analysis of deviation from Hardy–Weinberg equilibrium, estimation of linkage disequilibrium(LD) between polymorphisms, association of haplotypes with TG/HDL- C ratio and LDL-C/HDL-C ratio were performed using SNPStats.Results1.Both rs135539, rs3856806, rs3856806 and rs1805192 were significantly associated with an increased level of TG/HDL-C ratio, Difference(95% CI) values were 0.30(0.03~ 0.56), 0.91(0.59~ 1.23), 0.41(0.15~ 0.67) and 0.75(0.49~1.01). Whereas rs1800206 was significantly associated with a decreased level of LDL-C/HDL-C ratio, Difference(95% CI) values was-0.12(-0.19~-0.05). However, the other four SNPs in PPARs did not exhibit any significant association with TG/HDL- C ratio or LDL-C/HDL-C ratio after covariates adjustment.2. GMDR model showed that the significant models included a two-locus, a three-locus, a five-locus, a seven-locus and an eight-locus model on TG/HDL-C ratio. GMDR model showed that the significant models included a three-locus, a six-locus, seven-locus and an eight-locus model on LDL-C/HDL-C ratio. The eight-locus model including rs135539, rs1800206, rs4253778 in PPARα and rs10865710, rs1805192, rs3856806, rs709158, rs4684847 in PPARγ, had the highest level of prediction accuracy(63.3%), and displayed a better cross-validation consistency(10/10).3. Results of haplotype ananlysis indicated that A-V-G haplotype in PPARα(rs135539, rs1800206 and rs4253778) and C-P-T-A-C, C-A-C-A-C haplotype in PPARγ(rs10865710, rs1805192, rs4684847, rs709158 and rs3856806) were associated with an increased TG/HDL-C ratio. A-V-G haplotype in PPARα(rs135539, rs1800206 and rs4253778) was associated with a decreased LDL-C/HDL-C ratio. G-P-C-A-C, C-P-C-G-C and C-A-C-A-C haplotype were associated with a decreased LDL-C/HDL-C ratio.Conclusions1. Rs135539, rs1800206 in PPARα and rs3856806, rs1805192 in PPARγ were associated with TG/HDL-C ratio. Rs1800206 in PPARα was associated with LDL-C/HDL-C ratio.We did not found the association of other four SNPs and TG/HDL- C ratio or LDL-C/HDL-C ratio.2. The significant models included a two-locus, a three-locus, a five-locus, a seven-locus and an eight-locus model on TG/HDL-C ratio(P<0.05).We also found a significant interaction among rs135539, rs1800206, rs4253778, rs10865710, rs1805192, rs3856806, rs709158 and rs4684847 on LDL-C/HDL-C ratio(P<0.05).3. A-V-G haplotype in PPARα(rs135539, rs1800206 and rs4253778) and C-P-T-A-C, C-A-C-A-C haplotype in PPARγ(rs10865710, rs1805192, rs4684847, rs709158 and rs3856806) were associated with TG/HDL- C ratio. A-V-G haplotype in PPARα(rs135539, rs1800206 and rs4253778) and G-P-C-A-C, C-P-C-G-C and C-A-C-A-C haplotype in PPARγ(rs10865710, rs1805192, rs4684847, rs709158 and rs3856806) were associated with LDL-C/HDL-C ratio.