Introduction:
Gestational diabetes mellitus (GDM) and hypothyroidism are common pregnancy-related disorders that may have a genetic background. The hexokinase domain containing 1 (HKDC1) gene is involved in glucose metabolism, and its variants may influence thyroid function by modulating metabolic pathways. This interaction could contribute to the development of thyroid dysfunction.

Material and methods:
A total of 20 healthy pregnant controls, 20 pregnant women with GDM, and 19 pregnant women with hypothyroidism were genotyped for the HKDC1 gene polymorphisms rs1076224, rs4746822, rs2394529, and rs9645501.

Results:
Statistically significant differences were found in the genotype distribution of the HKDC1 rs1076224 polymorphism in the dominant model (G/G vs. A/G + A/A) between women with and without GDM (p = 0.039). Additionally, the HKDC1 rs4746822 polymorphism showed significant differences in both the codominant (p = 0.044) and overdominant (p = 0.014) models between hypothyroid and non-hypothyroid pregnant women. The rs2394529 polymorphism also demonstrated significant differences in the overdominant model (C/C + G/G vs. C/G, p = 0.032) between hypothyroid and non-hypothyroid groups. However, no differences were observed in the genotype or allele frequencies of the HKDC1 rs9645501 variant across the study groups.

Conclusions:
This study suggests a potential genetic association between HKDC1 polymorphisms and the risk of GDM and hypothyroidism in pregnancy. The findings highlight rs1076224 as a significant marker for GDM susceptibility, and rs4746822 and rs2394529 as potential markers for hypothyroidism. Further large-scale studies are needed to confirm these associations and understand their clinical implications.