Abstract
Type 2 diabetes mellitus (T2DM) is a complex disease caused by the interaction between genetic and environmental factors. A growing number of evidence suggests that the peroxisome proliferator-activated receptor gamma (PPARG) gene plays a major role in T2DM development. Meta-analysis of genetic association studies is an efficient tool to gain a better understanding of multifactorial diseases and potentially to provide valuable insights into gene-disease interactions. The present study was focused on assessing the association between Pro12Ala variation in the PPARG and T2DM risk through a comprehensive meta-analysis. We searched PubMed, WoS, Embase, Scopus and ProQuest from 1990 to 2017. The fixed-effect or random-effect model was used to evaluate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) depending on the heterogeneity among studies. The sources of heterogeneity and publication bias among the included studies were assessed using I2 statistics and Egger's tests. A total of 73 studies, involving 62,250 cases and 69,613 controls were included. The results showed that the minor allele (G) of the rs1801282 variant was associated with the decreased risk of T2DM under different genetic models. Moreover, the protective effect of minor allele was detected to be significantly more in some ethnicities including the European (18%), East Asian (20%), and South East Asian (18%). And the reduction of T2DM risk in Ala12 carriers was stronger in individuals from North Europe rather than Central and South Europe. Our findings indicated that the rs1801282 variant may contribute to decrease of T2DM susceptibility in different ancestries.
Highlights
Type 2 diabetes mellitus (T2DM) is a complex disease caused by the interaction between genetic and environmental factors
120 studies were excluded for different reasons (56 studies had not sufficient or relevant data about T2DM including studies that evaluated the association of Pro12Ala with type 1 diabetes, metabolite traits, or diabetes complications, assessed the link of other SNPs and genes with T2DM, and Genome-wide association studies (GWASs) studies ; 15 studies were not English studies or not available full text; 34 studies were the exclusion of study design such as a clinical trial, cohort, case-series, family-based studies, review and meta-analysis, letter to editors/research letters, meeting abstract, commentary, report, news, pilot study; and 15 studies were duplicate) that details are provided in Supplementary Table S1 online
Genomic association studies help in disease predispositions by using genomic variants which have been discovered by G WASs10
Summary
Type 2 diabetes mellitus (T2DM) is a complex disease caused by the interaction between genetic and environmental factors. The present study was focused on assessing the association between Pro12Ala variation in the PPARGand T2DM risk through a comprehensive meta-analysis. The results showed that the minor allele (G) of the rs1801282 variant was associated with the decreased risk of T2DM under different genetic models. Many Genome-wide association studies (GWASs) identified several candidate genes, including peroxisome proliferator-activated receptor gamma (PPARG), a member of the nuclear hormone receptor superfamily, as susceptible to T2DM loci in Finnish and British/Irish ancestries[11,12]. There is a lot of information about the genetic architecture of T2DM including the high degree of polygenicity and the tiny effect sizes of most genetic risk variants but several obstacles complicate translation process of these novel loci[13]. The missense variant rs1801282 ( known as Pro12Ala) in the exon B leads to an amino acid change from Proline (P) to Alanine (A) have been extensively reviewed in epidemiologic studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
