Genetic Variants in the FTO Gene and Their Association with Type 2 Diabetes Risk - A Meta-Analysis

Soumya Abraham ¹, Swati Paliwal ², Mohammad Chand Jamali ³*

This study elucidates the genetic contributions to T2DM, highlighting the FTO gene's variants and their implications for precision medicine approaches.

Abstract

Background: The global prevalence of type 2 diabetes mellitus (T2DM) is projected to rise significantly, with an estimated increase from 536.6 million cases in 2021 to 783.2 million by 2045. Genetic predisposition plays a crucial role in T2DM susceptibility, with the FTO gene, particularly the single nucleotide polymorphism (SNP) rs11076023, being linked to the disease. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar to identify relevant studies that examined the association between the FTO gene rs11076023 polymorphism and T2DM. Case-control studies published until December 31, 2023, were included, adhering to PRISMA guidelines. Data extraction was performed systematically, and statistical analysis was conducted using MetaGenyo to assess the association across various genetic models. Results: The meta-analysis encompassed three studies involving 3,887 participants (1,985 cases and 1,902 controls). The findings demonstrated a significant association between the T allele of rs11076023 and increased T2DM risk, particularly within the recessive genetic model (TT vs. TA + AA), indicating a higher susceptibility among individuals with the TT genotype. In contrast, the over-dominant model suggested a protective effect associated with the TA heterozygous genotype. Notable heterogeneity was observed across the studies, and sensitivity analyses confirmed the robustness of the associations. Conclusion: This meta-analysis highlights the FTO gene rs11076023 polymorphism as a significant genetic factor influencing T2DM susceptibility, particularly within certain population subsets. The findings underscore the complexity of T2DM risk, emphasizing the interplay between genetic factors and lifestyle choices. Further research with larger, diverse populations is necessary to validate these associations and explore the underlying biological mechanisms, which may inform targeted interventions for T2DM prevention and management.

Keywords: Type 2 Diabetes, FTO gene, SNP rs11076023, genetic association, population-specific risk

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