Recurrent miscarriage occurs 2.2 more often if poor Vitamin D Receptor – Aug 2019

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

J Matern Fetal Neonatal Med. 2019 Aug 25:1-281. doi: 10.1080/14767058.2019.1660768.
Barišić A1, Pereza N1, Hodžić A2, Gašparović Krpina M3, Ostojić S1, Peterlin B2.
1 Faculty of Medicine, University of Rijeka, Department of Medical Biology and Genetics , Rijeka , Croatia.
2 Clinical Institute of Medical Genetics, UMC , Ljubljana , Slovenia.
3 Clinical Hospital Center "Rijeka", Department of Obstetrics and Gynecology , Rijeka , Croatia.

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Purpose: 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 approximately 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 the present study was to assess whether maternal VDR SNPs are associated with the risk of RPL in Slovenian and Croatian women.

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

Results: We found a statistically significant higher frequency of the rs222857 CC genotype (X2 = 6.61, p = 0.036) and C allele (X2 = 5.93, p = 0.015) in RPL women compared to controls. Subsequently, the odds for RPL for the rs222857 were increased under the recessive (CCvsCT + TT: OR = 1.78; 95% CI = 1.12-2.82; p = 0.015) and the codominant (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) genetic models. The other two analyzed polymorphisms did not show any statistical significant result.

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

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Poor VDR increases recurrent miscarriage risk by 1.5 X - Feb 2021

Vitamin D receptor gene polymorphisms and haplotypes in the etiology of recurrent miscarriages
Sci Rep . 2021 Feb 25;11(1):4646. doi: 10.1038/s41598-021-84317-3.
Hubert Wolski 1 2, Grażyna Kurzawińska 1 3, Marcin Ożarowski 4, Aleksandra E Mrozikiewicz 5, Krzysztof Drews 1, Tomasz M Karpiński 6, Anna Bogacz 7 8, Agnieszka Seremak-Mrozikiewicz 1 3 7
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A few years ago it was shown that disturbed metabolism of the vitamin D/receptor (VD/VDR) complex may be important in the etiology of spontaneous abortion, as well as in the etiology of recurrent miscarriages (RM). The goal of this study was to investigate the association between four maternal VDR polymorphisms as well as haplotypes settings and RM occurrence in a Polish population of women in reproductive age. A total of 230 women were recruited to this study (110 with RM, 120 consecutively recruited age-matched healthy women with at least two full-term pregnancies and with no history of miscarriages). DNA samples were genotyped for VDR polymorphisms: FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236). Significant differences in genotype distributions and allele frequencies between case and control groups were observed in VDR BsmI polymorphism (GG vs. GA and AA, OR = 0.56, p = 0.036 and OR = 1.49, p = 0.035, respectively). The best evidence of an association with RM prevention was observed for the TTGT haplotype, which was more frequent among controls than cases even after permutation test (0.09 vs. 0.017, p = 0.0024). Other haplotypes were also significantly more frequent in the control group: TGT (rs7975232, rs1544410, rs2228570), TG (rs7975232, rs1544410), TTG (rs731236, rs7975232, rs1544410), TT (rs731236, rs7975232). Our research indicated the possible role of VDR BsmI genetic polymorphism in RM etiology, suggesting at the same time the active role of maternal VD metabolism and its influence on pregnancy outcome. The significant influence of several maternal haplotypes was shown to prevent RM occurrence.