Background: This study aims to investigate the genetic contribution of polymorphic variants of the TCF7L2 (rs7903146) and PPARG (rs1801282) genes to the risk of developing prediabetes in individuals of Kazakh ethnicity. Materials and Methods: This was a case-control study involving 200 cases with prediabetes and 200 prediabetes-free controls, aged 16–60 years (n = 400). Real-time polymerase chain reaction on a StepOnePlus instrument (Applied Biosystems, USA), employing the TaqMan method for site-specific amplification and genotyping of the TCF7L2 (rs7903146) and PPARG (rs1801282) genes was used. Results: Patients with prediabetes had a higher birth weight, increased BMI, larger waist and hip circumferences, and a higher waist-to-hip ratio compared to healthy patients in the control group. There was a significant increase in the risk of developing prediabetes for both the rs1801282 polymorphism of the PPARG gene and the rs7903146 polymorphism of the TCF7L2 gene. The risk was 9.8 times higher in carriers of the GG genotype of PPARG (rs1801282) (OR = 9.769, 95% CI: 2.124–44.922, p = 0.003) and 10.7 times higher for carriers of the TT genotype of TCF7L2 (rs7903146) (OR = 10.731, 95% CI: 1.309–87.939, p < 0.001). Conclusions: These findings highlight the need for tailored early screening and preventive strategies for prediabetes in the Kazakh population, focusing on individuals with high-risk genotypes. Such efforts could improve targeted interventions and reduce the burden of prediabetes. Future research should adopt a longitudinal design, include diverse ethnic groups, and investigate additional genetic markers to provide a more comprehensive understanding of the genetic underpinnings of prediabetes.

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.