Genetic determinants of type 2 diabetes mellitus: The role of FABP2, PNPLA3, FADS1, LEPR, and GCKR gene polymorphisms in Russians and Yakuts

A comparative analysis of the role of gene polymorphisms associated with lipid and carbohydrate metabolism (FABP2 rs1799883, PNPLA3 rs738409, FADS1 rs174537, LEPR rs1137101, GCKR rs780094) in the development of type 2 diabetes mellitus (T2DM) in Russian (n=179) and Yakut (n=446) populations of the Republic of Sakha (Yakutia) using a case-control study was conducted. Using PCR-RFLP genotyping significant interpopulation differences were identified in the distribution of FABP2, PNPLA3, FADS1, and LEPR gene alleles, reflecting their potential adaptive role to different environmental conditions. The main finding was a pronounced ethnic specificity for the FABP2 Ala54Thr polymorphism: in Yakuts, the heterozygous Ala/Thr genotype was identified as a risk factor for T2DM (OR = 1.68; p = 0.01), while the homozygous Thr/Thr variant exhibited a protective effect (OR = 0.51; p < 0.001). No significant association was found in the Russian sample. Analysis of biochemical parameters in T2DM patients revealed genotype-dependent differences in lipid profile, fasting glucose levels, and liver function markers, confirming the role of the studied genes as modifiers of the metabolic phenotype.

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