Abstract
OBJECTIVE: The purpose of this study was to assess associations between iron homeostasis-related gene polymorphisms and gestational diabetes mellitus (GDM), adverse pregnancy outcomes, and neonatal outcomes. METHODS: In total, 138 patients with GDM and 74 normal pregnancy controls were recruited. Time-of-flight mass spectrometry was used to genotype single-nucleotide polymorphisms (H63D rs1799945, TMPRSS6 rs855791, GDF15 rs1059369, rs4808793, BMP2 rs173107, C282Y rs3811647, rs1800562, rs269853, TF rs8177240, TFR2 rs7385804, FADS2 rs174577, and CUBN rs10904850) in 12 candidate genes related to iron homeostasis. Adverse pregnancy outcomes and neonatal health data were collected. Differences in genotype distributions and allele frequencies between patients and controls as well as their correlations with clinical factors were assessed. Additionally, associations between genotype, haemoglobin levels, and ferritin levels were evaluated. RESULTS: Pregnant women carrying the GDF15 rs4808793 allele (C) or TMPRSS6 rs855791 homozygous mutation (GG) had a significantly higher risk of GDM than that in the control group (p < 0.05). In patients with GDM, the BMP2 rs173107 heterozygous mutation (AC) was associated with significantly higher haemoglobin levels in late pregnancy compared with those for wild-type (AA) BMP2 (p < 0.05). Furthermore, in patients with GDM, the FADS2 rs174577 heterozygous mutation (AC) was associated with a significantly reduced risk of preterm birth (p < 0.05), the H63D rs1799945 heterozygous mutation (CG) was associated with a significantly increased risk of adverse neonatal outcomes (p < 0.05), TFR2 rs7385804 was associated a significantly reduced probability of caesarean section (p < 0.05), and the G mutation in TMPRSS6 rs855791 was related to a significantly increased probability of caesarean section (p < 0.05). CONCLUSIONS: These results suggest that polymorphisms in genes related to iron metabolism could potentially impact pregnancy and neonatal outcomes in patients with GDM. Large-scale studies are needed to further clarify the relationship between these polymorphisms and susceptibility to GDM.