Genetic variation in the maternal vitamin D receptor FokI gene as a risk factor for recurrent pregnancy loss

Recurrent pregnancy loss (RPL) is a reproductive disorder defined as the loss of two or more pregnancies before 24 weeks of gestation. Despite the fact that several mechanisms have been previously described for the pathogenesis of RPL, the causes of ∼50% of cases remain unknown. However, recent studies indicate association of vitamin D deficiency with adverse pregnancy outcome, including RPL. The vitamin D receptor (VDR) is a crucial mediator of the pleiotropic cellular effects of vitamin D. Its function is influenced by several single nucleotide polymorphisms (SNPs). The main objective of this study is to assess whether maternal VDR SNPs are associated with the risk of RPL in Slovenian and Croatian women.

A case-control study including 320 women with RPL and control women is designed to examine the potential association of VDR polymorphisms (FokI rs222857, Cdx2 rs11568820, and Taq1 rs731236) with RPL. Genotyping is performed using polymerase chain reaction and restriction fragment length polymorphism methods.

We find a statistically significant higher frequency of the rs222857 CC genotype (χ² = 6.61, p = .036) and C allele (χ² = 5.93, p = .015) in RPL women compared to controls. Subsequently, the odds for RPL for the rs222857 are increased under the recessive (CCvsCT + TT: OR = 1.78; 95% CI = 1.12-2.82; p = .015) and the codominant (CCvsTT: OR = 2.21; 95% CI = 1.08-4.53; p = .029; CCvsCT: OR = 1.68; 95% CI = 1.04-2.72; p = .036) genetic models. The other two analyzed polymorphisms did not show any statistical significant result.

Our results suggest that variations in the maternal VDR FokI gene might be associated with RPL in Slovenian and Croatian women.