THADA, SDHAF4, and MACF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes

Gestational diabetes mellitus (GDM) is a metabolic disorder in pregnant women leading to various complications. Consequently, factors predisposing its development are being sought. Previous studies have shown that the pathogenesis of GDM is similar to that of type 2 diabetes, and it is therefore thought that the two diseases may have a common genetic basis. The aim of this study was to examine the associations between thyroid adenoma-associated (THADA) rs7578597 T>C, succinate dehydrogenase complex assembly factor 4 (SDHAF4) rs1048886 A>G, and microtubule-actin crosslinking factor 1 (MACF1) rs2296172 A>G gene polymorphisms and the risk of GDM development as well as selected clinical parameters in women with GDM. We also examined the expression of these genes in the placenta of women with and without GDM in association with clinical parameters. This case-control study included 272 pregnant women with GDM and 348 pregnant women with normal glucose tolerance. There were no statistically significant differences in the distribution of the THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G gene polymorphisms between pregnant control women and women with GDM. The associations between clinical parameters such as body mass before pregnancy, body mass at birth, body mass increase during pregnancy, BMI before pregnancy, BMI at birth, BMI increase during pregnancy, glycated hemoglobin (HbA1c), daily insulin requirement, childbirth time, and newborn body mass and APGAR score, and the THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G genotypes were statistically non-significant. We only observed lower values of body mass before pregnancy and body mass at birth in women with the SDHAF4 rs1048886 AG genotype in comparison with AA genotype carriers. There was no statistically significant difference in the expression of THADA, SDHAF4, and MACF1 genes in the placenta between women with GDM and healthy women. There were also no statistically significant correlations between THADA, SDHAF4, and MACF1 gene expression in the placenta and clinical parameters. The results of our study suggest that THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G gene polymorphisms are not significant factors associated with GDM onset. In addition, SDHAF4 rs1048886 A>G may be associated with body mass before pregnancy and body mass at birth in pregnant women.

Automated summary

This study aimed to investigate the associations of THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G gene polymorphisms with the development of gestational diabetes mellitus (GDM) and their relationships with clinical parameters. The results showed no significant associations between these gene polymorphisms and the onset of GDM, but SDHAF4 rs1048886 A>G may be associated with pre-pregnancy body weight and birth weight in pregnant women.