Comprehensive Snp-Based Evaluation of Fat Mass and Obesity-Associated Gene (Fto) Variants and Their Association With Type 2 Diabetes: Bushehr Elderly Health (Beh) Program Publisher



Alipour N ; Farsi F ; Amrollahi Bioky A ; Tavasoli N ; Bidkhori M ; Sehatpour F ; Khalagi K ; Fahimfar N ; Ebrahimpur M ; Ostovar A ; Nabipour I ; Hasanzad M ; Larijani B
Source: Journal of Diabetes and Metabolic Disorders Published:2025

Abstract

Purpose: This study aimed to investigate the association between fat mass and obesity-associated (FTO) gene Single Nucleotide Polymorphisms (SNPs) and the risk of type 2 diabetes (T2DM) in older Iranian adults, addressing the limited data available for older populations in the Middle East. Methods: We analyzed 2,192 older adults from the Bushehr Elderly Health program in southern Iran. T2DM was defined using American Diabetes Association ADA criteria. The Illumina Global Screening Array was used to genotype FTO SNPs. In our analysis, 1,146 SNPs were examined for association with type 2 diabetes using generalized linear models under additive, dominant, and recessive models, controlling for age and sex, following quality control and linkage disequilibrium pruning. False discovery rate (FDR) correction was applied, with significance set at PFDR < 0.05. Results: Among 2,192 elderly participants, 34% had type 2 diabetes. Although none of the examined FTO SNPs showed a statistically significant association with T2DM after FDR correction, the lowest P value was observed for rs16952649 under the additive model (P ≈ 0.002). Known risk alleles, such as rs1421085 (C allele: 42% vs. 43% in Europeans) and rs9940128 (A allele: 45% vs. 44%), were present at similar frequencies to European populations. Ethnic-specific genetic patterns were also observed in the Bushehr cohort. Conclusion: T2DM was not significantly associated with FTO variants, indicating context-dependent effects that were probably influenced by adiposity. The necessity of population-specific genetic research is highlighted by these findings. © 2025 Elsevier B.V., All rights reserved.