Analysis On The Association Of Polymorphisms Of PPARδ/γ Gene And Its Interaction With Obesity On The Level Of LDL-C

Objective1. To explore the association between PPARδ/γ gene polymorphisms and the level of LDL-C2. To detect the possible gene-gen interaction among the PPARδ/γ gene polymorphisms on the LDL-C3. To explore the association between PPARδ/γ gene haplotypes and LDL-C so as to refine the SNP-phenotype association4. To explore the possible interactive effect of PPARδ/γ gene haplotypes along with common obesity and central obesity on LDL-CMethods1. The study population were recruited from the Prevention of Multiple metabolic disorders and Metabolic syndrome in Jiangsu province(PMJMS). A total of 820 unrelated individuals were randomly selected for the Taqman genotyping of PPARδ/γ gene.2. We used the SNPAssoc package to analyse the association between the SNPs of PPARδ/γ gene and the level of LDL-C.3. MB-MDR was used to detect the potential gene-gene interactions among the polymorphisms involved.4. Haplo.score was used to test the association between PPARδ/γ gene haplotypes and LDL-C5. Haplo.glm was available to explore the interaction between PPARδ/γ gene haplotypes and common/central obesity on LDL-CResults1. We found that rs9794, rs10865710, rs1085192, rs709158 and rs3856806 were significantly associated with the level of LDL-C(P<0.05), among which all the SNPs showed a positive effect on the LDL-C except rs10865710 which presented a negative effect. After multiple testing, the association between rs1085192/rs709158/ rs3856806 and LDL-C remains statistically significant(P<0.007).2. Significant gene-gene interactions among the SNPs of PPARδ/γ genes were detected. We performed permutation test on the Wmax based on 1000 permutations and found that all the 2 to 7-locus models were significant(P<0.05).3. The T-G haplotype of PPARδ gene was positively associated with LDL-C;several PPARγ haplotypes were also statistically associated with LDL-C, including G-P-C-A-C(P<0.001), C-P-C-A-C(P=0.012), C-P-T-A-C(P=0.025), C-P-C-G-C(P=0.029), G-A-C-A-T(P=0.025), C-A-C-A-C(P=0.022), C-A-C-A-T(P=0.006), C-A-C-G-C(P=0.002) and C-A-C-G-T(P<0.001).4. We used LDL-C as the phenotype to fit the model none of the PPARδhaplotypes have significant interactive effect with either common obesity or central obesity after adjustment of alcohol drinking(P>0.05); while the results showed that PPARγ haplotypes G-P-T-G-T and C-A-C-G-T were involved in an interactive effect with common obesity on LDL-C(P>0.05), while C-P-C-G-T was involved with an interactive effect with central obesity on LDL-CConclusion1. PPARδ/γ gene polymorphisms(rs9794, rs10865710, rs1085192, rs709158 and rs3856806) were significantly associated with LDL-C2. There was a significant gene-gene interaction among the SNPs of PPARδ/γgenes.3. The PPARδ haplotype T-G were associated with LDL-C; while the PPARγhaplotype G-P-C-A-C, C-P-C-A-C, C-P-T-A-C, C-P-C-G-C, G-A-C-A-T, C-A-C-A-C, C-A-C-A-T, C-A-C-G-C and C-A-C-G-T were also associated with the level of LDL-C.4. We didn’t find the interaction between PPARδ haplotypes and common/centralobesity on LDL-C.5. PPARγ haplotypes G-P-T-G-T and C-A-C-G-T had an interactive effect with common obesity on LDL-C; while C-P-C-G-T had an interactive effect with central obesity on LDL-C...