G Allele of the rs1801282 Polymorphism in PPARγ Gene Confers an Increased Risk of Obesity and Hypercholesterolemia, While T Allele of the rs3856806 Polymorphism Displays a Protective Role Against Dyslipidemia: A Systematic Review and Meta-Analysis

BACKGROUND: The relationships between the rs1801282 and rs3856806 polymorphisms in nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) gene and obesity indexes as well as serum lipid levels have been extensively investigated in various studies, but the results were inconsistent and even contradictory. METHODS: PubMed, Google Scholar, Embase, Cochrane Library, Web of Science, Wanfang, CNKI and VIP databases were searched for eligible studies. The random-effTPDEects model was used, and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to estimate the differences in obesity indexes and serum lipid levels between the subjects with different genotypes in a dominant model. Heterogeneity among studies was assessed by Cochran’s x(2)-based Q-statistic test. Publication bias was identified by using Begg’s test. RESULTS: One hundred and twenty studies (70,317 subjects) and 33 studies (18,353 subjects) were identified in the analyses for the rs1801282 and rs3856806 polymorphisms, respectively. The G allele carriers of the rs1801282 polymorphism had higher levels of body mass index (SMD = 0.08 kg/m(2), 95% CI = 0.04 to 0.12 kg/m(2), p < 0.001), waist circumference (SMD = 0.12 cm, 95% CI = 0.06 to 0.18 cm, p < 0.001) and total cholesterol (SMD = 0.07 mmol/L, 95% CI = 0.02 to 0.11 mmol/L, p < 0.01) than the CC homozygotes. The T allele carriers of the rs3856806 polymorphism had lower levels of low-density lipoprotein cholesterol (SMD = -0.09 mmol/L, 95% CI = -0.15 to -0.03 mmol/L, p < 0.01) and higher levels of high-density lipoprotein cholesterol (SMD = 0.06 mmol/L, 95% CI = 0.02 to 0.10 mmol/L, p < 0.01) than the CC homozygotes. CONCLUSIONS: The meta-analysis suggests that the G allele of the rs1801282 polymorphism confers an increased risk of obesity and hypercholesterolemia, while the T allele of the rs3856806 polymorphism displays a protective role against dyslipidemia, which can partly explain the associations between these polymorphisms and cardiovascular disease. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier [CRD42022319347].