Association of Genetic Polymorphisms with Gestational Diabetes in a Kazakh Population: A Case–Control Study
Danyarova L. Svyatova G. Berezina G. Tuleutayev R. Sultanova B. Taigulova A. Sartayeva A. Zhekeyeva M. Karibayeva I.
March 2026Multidisciplinary Digital Publishing Institute (MDPI)
Diagnostics
2026#16Issue 5
Background: Gestational diabetes mellitus (GDM) poses a growing public health challenge worldwide due to its increasing prevalence, associated pregnancy complications, and long-term metabolic risks for both mothers and offspring. Genetic factors are known to contribute to GDM susceptibility, yet little is known about their relevance in ethnic Kazakh population. The primary objective of this study was to evaluate associations between selected candidate SNPs involved in β-cell function and the risk of GDM in a Kazakh cohort. Secondary objectives included the assessment of potential gene–gene interactions. Methods: We conducted a case–control study among 365 pregnant Kazakh women. Of these, 217 were diagnosed with GDM, and 148 had normal glucose tolerance. Clinical and genealogical data were collected. Eight candidate SNPs that were previously associated with GDM or glucose metabolism were genotyped. Logistic regression was used to assess associations between SNPs and GDM risk. Gene–gene interactions were evaluated using multifactor dimensionality reduction (MDR). Results: In univariate analysis, MTNR1B rs10830963 demonstrated a statistically significant association under the additive model (OR 0.61, 95% CI 0.42–0.89), indicating a potential protective effect of the C allele. However, this association was not statistically significant after multivariable adjustment (adjusted OR 0.58, 95% CI 0.32–1.03) and correction for multiple testing. In the adjusted analysis, TCF7L2 rs7903146 showed a significant association under the dominant model (adjusted OR 2.29, 95% CI 1.01–5.46); however, this finding did not remain significant following FDR correction. MDR analysis showed that the best two-locus model included IGF2BP2 rs4402960 and CDKAL1 rs7754840 (CVC = 6/10; testing accuracy = 0.558; permutation p < 0.001). The most stable interaction was observed for the three-locus model comprising IGF2BP2 rs4402960, MTNR1B rs10830963, and PPARG rs1801282 (CVC = 9/10; testing accuracy = 0.576; permutation p < 0.001). Conclusions: The findings suggest that common variants in IGF2BP2, CDKAL1, MTNR1B, TCF7L2, PPARG, and GCK do not exert strong individual effects on GDM susceptibility in this cohort of ethnic Kazakh women. Instead, the results are more consistent with a modest polygenic architecture characterized by small effect sizes and possible weak gene–gene interactions. MDR analysis identified statistically significant interaction models; however, their limited predictive accuracy indicates that these findings should be interpreted as exploratory.
case–control study , CDKAL1 , genetic polymorphisms , gene–gene interaction , gestational diabetes mellitus , glucose metabolism , IGF2BP2 , Kazakh population , single-nucleotide polymorphisms
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National Center of Endocrinology and Diabetes, JSC Research Institute of Cardiology and Internal Diseases, Almaty, 050012, Kazakhstan
Scientific Department of the Center for Molecular Medicine, Center for Molecular Medicine, Almaty, 050026, Kazakhstan
Department of Strategy and Science, JSC Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, 050020, Kazakhstan
JSC Research Institute of Cardiology and Internal Diseases, Almaty, 050000, Kazakhstan
Department of Internal Medicine, Division of Graduate and Continuing Education, JSC Research Institute of Cardiology and Internal Diseases, Almaty, 050000, Kazakhstan
Department of Pediatrics, Semey Medical University, Semey, 071400, Kazakhstan
Department of General Medical Practice No. 2, West Kazakhstan Marat Ospanov Medical University, Aktobe, 030000, Kazakhstan
Department of Health Policy and Community Health, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, 30460, GA, United States
National Center of Endocrinology and Diabetes
Scientific Department of the Center for Molecular Medicine
Department of Strategy and Science
JSC Research Institute of Cardiology and Internal Diseases
Department of Internal Medicine
Department of Pediatrics
Department of General Medical Practice No. 2
Department of Health Policy and Community Health
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