Association between PPAR-γ (rs1801282) polymorphism and susceptibility to obesity and type 2 diabetes mellitus: a meta-analysis with trial sequential analysis

Background peroxisome proliferator-activated receptor-γ (PPAR-γ) plays a pivotal role in lipid homeostasis and insulin signaling; however, the association of its PPAR-γ rs1801282 polymorphism with obesity and type 2 diabetes mellitus (T2DM) remains controversial. Methods We searched PubMed, Web of Science, CNKI and WanFang up to September 2025. Meta-analysis was conducted across five genetic models, with Odds Ratio (OR) and 95% Confidence Interval (95% CI) assessing rs1801282 association with obesity/T2DM susceptibility. Sensitivity analysis and trial sequential analysis (TSA) were performed to verify the reliability of our findings.This meta-analysis was registered in PROSPERO (CRD420261297714). Results A total of 24 studies involving 6739 cases and 7337 controls were included in this meta-analysis. PPAR-γ (rs1801282) C allele was significantly associated with increased overall obesity risk (OR = 2.339, 95% CI: 1.418–3.864, P = 0.001) and it was strongly correlated with obesity in Caucasian populations whereas in Asian populations it tended to elevate obesity risk but was based on only one study. For T2DM, no significant association was observed between the rs1801282 polymorphism and overall disease risk (OR = 0.975, 95% CI: 0.827–1.148, P  = 0.759), though a marginally significant association was detected in the Asian subgroup under the dominant model (OR = 0.740, 95% CI: 0.551–0.994, P  = 0.046). No significant associations were found in other ethnic groups or genetic models (all P  > 0.05). Trial sequential analysis (TSA) confirmed the reliability of the conclusions regarding the association between rs1801282 and obesity/T2DM in Asian populations. Conclusions In conclusion, the PPAR-γ rs1801282 C allele is significantly associated with increased obesity risk and shows a marginally significant association with T2DM in Asians under the dominant model, but no consistent link with overall T2DM risk.