The joint effect of PPARG upstream genetic variation in association with long-term persistent obesity: Tehran cardio-metabolic genetic study (TCGS).

This study is the first study that aims to assess the association between SNPs located at the PPARG gene with long term persistent obesity. In this cohort association study, all adult individuals who had at least three consecutive phases of BMI (at least nine years) in Tehran genetic Cardio-metabolic Study (TCGS) were included. Individuals who always had 30 ≤ BMI < 35 and individuals who always had 20 < BMI ≤ 25 were assigned to the long-term persistent obese group and persistent normal weight group, respectively. Other individuals were excluded from the study. We used four gamete rules to make SNP sets from correlated nearby SNPs and kernel machine regression to analyze the association between SNP sets and persistent obesity or normal weight. The normal group consisted of 1547 individuals with the mean age of 40 years, and the obese group consisted of 1676 individuals with mean age of 48 years. Two groups had a significant difference between all measured clinical characteristics at entry time. The kernel machine result shows that nine correlated SNPs located upstream of PPARG have a significant joint effect on persistence obesity. This is the first study on the association between PPARG variants with persistent obesity. Three of the nine associated markers were reported in previous GWAS studies to be associated with related diseases. For the studied markers in the PPARG gene, the Iranian allele frequency was near the American and European populations. Case–control analytic study.