Genetic Predisposition to Prediabetes in the Kazakh Population.

Abstract

The aim of this study was to conduct a comparative analysis of the population frequencies of the minor allele of polymorphic variants in the genes TCF7L2 (rs7903146) and PPARG (rs1801282), based on the genome-wide association studies analysis data associated with the risk of developing prediabetes, in an ethnically homogeneous Kazakh population compared to previously studied populations worldwide. This study utilized a genomic database consisting of 1800 ethnically Kazakh individuals who were considered in healthy condition. Whole-genome genotyping was performed using Illumina OmniChip 2.5-8 arrays, which interrogated approximately 2.5 million single nucleotide polymorphisms. The distribution of genotypes for the TCF7L2 (rs7903146) and PPARG (rs1801282) polymorphisms in the Kazakh sample was found to be in Hardy-Weinberg equilibrium (p > 0.05). The minor G allele of the "Asian" protective polymorphism rs1801282 in the PPARG gene was observed at a frequency of 13.8% in the Kazakh population. This suggests a potentially more significant protective effect of this polymorphism in reducing the risk of prediabetes among Kazakhs. The frequency of the unfavorable T allele of the insulin secretion-disrupting gene TCF7L2 (rs7903146) in Kazakhs was 15.2%. Studying the associations of genetic markers for prediabetes enables the timely identification of "high-risk groups" and facilitates the implementation of effective preventive measures. Further results from replicative genomic research will help identify significant polymorphic variants of genes underlying the alteration of prediabetes status.