Body iron status is likely to be associated with type 2 diabetes (T2DM) and gestational diabetes mellitus (GDM); transmembrane protease serine 6 (TMPRSS6) polymorphisms may be associated with T2DM risk through their effects on body iron status. However, it remains unknown whether the TMPRSS6 single nucleotide polymorphisms (SNPs) affect the risk of GDM development. We aimed to determine whether the TMPRSS6 SNPs rs855791 (V736A) and rs4820268 (D521D) are associated with the risk of GDM in pregnant women. The two SNPs in TMPRSS6 gene were genotyped and examined for their associations with body iron status and GDM risk in 398 unrelated Chinese Han pregnant women. The 2 TMPRSS6 SNPs rs855791 and rs4820268 were both significantly associated with serum iron and transferrin saturation (P < 0.01 for all) rather than ferritin. After adjustment for covariates, the C allele of rs4820268 was nominally and significantly associated with an increased risk of GDM (OR = 2.531; 95%CI = 1.044-6.136, P = 0.040); when concentrations of ferritin were further adjusted, the association was still significant (OR = 2.528; 95%CI = 1.043-6.126, P = 0.040). There was a significant trend (P = 0.065) in the association between the T allele of rs855791 and an increased GDM risk in this study population. The 2 TMPRSS6 SNPs rs855791 and rs4820268 were both significantly associated with serum iron and transferrin saturation, and TMPRSS6 variants might be associated with the risk of GDM. Furthermore, the effects of TMPRSS6 SNPs on the risk of GDM may not be completely explained by the mediation of body iron status. Further studies are warranted.
Keywords: Body iron status; Gestational diabetes; Iron; Single nucleotide polymorphism; Transmembrane protease serine 6.