Single nucleotide polymorphisms of vitamin D receptor and recurrent pregnancy loss

Aim: Recurrent pregnancy loss (RPL) is a reproductive disorder defined as the loss of two or more pregnancies from the time of conception until 24 weeks of gestation. Despite the fact that several mechanisms have been previously described for the pathogenesis of RPL, the causes of approximately 50% remain unknown. However, recent studies indicate association of vitamin D with adverse pregnancy outcome, including RPL. The vitamin D receptor (VDR) is a crucial mediator of the pleiotropic cellular effects of vitamin D. It's function is influenced by several single nucleotide polymorphisms (SNPs). The main objective of the present study was to assess whether three different maternal VDR SNPs are associated with the risk of RPL in Slovenian and Croatian women. Methods: A case – control study including 320 women was designed to examine the potential association of VDR polymorphisms (FokI rs222857, Cdx2 rs115688 and Taq1 rs731236) with RPL. Genotyping was performed using PCR-RFLP methods. Results: We found a statistically significant higher frequency of the FokI rs222857 CC genotype (X2=6.61, P=0.036) and C allele (X2=5.93, P=0.015) in women with RPL compared to controls. Additionally, the odds for RPL were increased under the recessive (CCvsCT+TT: OR=1.78 ; 95% CI=1.12-2.82 ; P=0.015) and codominant genetic models (CCvsTT: OR=2.21 ; 95% CI=1.08-4.53 ; P=0.029 ; CCvsCT: OR=1.68 ; 95% CI=1.04-2.72 ; P=0.036). Furthermore, Taq1 rs731236 C allele showed a statistically significant higher frequency in women with RPL compared to controls (X2=4.13, P=0.042). Conclusion: Our results suggest that the CC genotype of the FokI rs222857 polymorphism in women might be a genetic marker for RPL.