Gene variants and haplotypes of Vitamin D biosynthesis, transport, and function in preeclampsia.

Abstract

Objective: To find whether the gene variants and haplotypes of cytochrome (CYP) 27B1 (1α-hydroxylase), group-specific component (GC) that is a vitamin D binding protein, vitamin D receptor (VDR), peroxisome proliferator-activated receptor γ (PPARγ) and retinoid-X receptor (RXR) affect the risk of preeclampsia. Methods: In a case-control study 100 women with preeclampsia and 100 healthy pregnant women were investigated for gene variants and haplotypes of vitamin D biosynthesis, transport, and function using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The frequency of gene variants of PPARγ Pro12Ala and RXR -α (A/G, rs749759) were not significantly different comparing patients and controls. The TT genotype of CYP 27B1 (G > T) was associated with 2.2-fold (95% CI 1.04-4.7, p = 0.039) increased risk of early-onset preeclampsia. Also, the TT genotype of GC rs7041 (T > G) increased the risk of preeclampsia [OR = 2.13 (95% CI 1.09-4.17, p = 0.027)]. The VDR ApaI GT genotype elevated susceptibility to preeclampsia (OR = 2.55, p = 0.04). Further, the presence of VDR ApaI GT+TT genotype was associated with higher levels of body mass index, and systolic blood pressure, and lower level of 25 (OH)-D3. In the presence of haplotype CYP T, VDR T, and RXR A (TTA) compared to haplotype GTG the risk of preeclampsia was 6.71-fold (p = 0.044). Conclusions: The present study indicated an association between the CYP 27B1, GC, and VDR ApaI variants with the risk of preeclampsia. Also, the variants of the latter polymorphism influenced BMI, blood pressure, and vitamin D levels.