FTO gene variants (rs9939609, rs8050136 and rs17817449) and type 2 diabetes mellitus risk: A Meta-Analysis

Background and aims: There is tremendous increase in type 2 diabetes mellitus (T2DM) worldwide. The impact of FTO gene polymorphisms on the risk of T2DM is not yet clear because of the controversial results of studies. This meta-analysis aimed to better clarify the association between three FTO gene polymorphisms SNPs (rs9939609, rs8050136 and rs17817449) and T2DM in a larger combined population worldwide. Material and methods: A comprehensive search on the PubMed, Science Direct, and Web of Science databases was conducted to identify investigations in relationship between different FTO gene polymorphisms (rs9939609, rs8050136 and rs17817449) and T2DM globally. Published papers from January 2007 to May 2023 were collected. Inclusion criteria are limited to human case-control studies published in English and peer-reviewed, which provided data on the genotype distributions of FTO gene polymorphisms and T2DM risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to express the results of the meta-analysis. Potential sources of bias and heterogeneity using Egger's regression analysis were also assessed. Results: Of 234695 identified articles, forty-eight studies were selected including 36,051 patients with T2DM and 51,266 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and rs9939609 FTO gene polymorphism in the Allele contrast (A vs. T: OR = 1,30, 95% CI = 1.14; 1.48, P < 0,05, I-2 = 0,94), Recessive model (AA vs. AT + TT: OR = 1,54, 95% CI = 1.19; 2.00, P < 0,05, I-2 = 0,94), Dominant model (AA + AT vs. TT: OR = 1,26, 95% CI = 1.10; 1.45, P < 0,05, I-2 = 0,89), homozygote model (AA vs. TT: OR = 1,60, 95% CI = 1.26; 2.03, P < 0,05, I-2 = 0,90), and heterozygote model (AA vs. AT: OR = 1,43, 95% CI = 1.09; 1.88, P = 0,008, I-2 = 0,93). we also found a significantly increased risk of T2DM susceptibility and rs8050136 FTO gene polymorphism under all models. For rs17817449 we did not find any association between with T2DM. Conclusion: The present meta-analysis confirms that rs9939609 and rs8050136 in the FTO gene are significantly associated with T2DM, while rs17817449 does not show any association.