Purpose: Vitamin D deficiency is common during pregnancy and may cause complications such as preterm labor (PTL). This study was aimed to investigate the effect of the vitamin D-binding protein (VDBP) rs7041 genotype, which has a significant effect on vitamin D metabolism and PTL.
Methods: This cross-sectional study was conducted with 32 pregnant women who had spontaneous PTL and 54 pregnant women who had no specific findings as a control group. Serum total vitamin D 25-hydroxy vitamin D (25(OH)D) levels were measured using the Elecsys Vitamin D Total Kit. VDBP was measured using a VDBP Quantikine ELISA Kit. The levels of bioavailable 25(OH)D were calculated based on the total 25(OH)D and VDBP concentrations. DNA was extracted using the DNeasy Blood and Tissue Kit. Single nucleotide polymorphisms (rs7041) in GC were analyzed using a TaqMan SNP Genotyping Assay Kit. The unpaired t-test, Chi-squared, and ANCOVA tests were performed. Firth's penalized logistic regression was applied. The area under the curve (AUC) was calculated and the cutoff value was determined. All statistical analyses were performed using R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria).
Results: Total 25(OH)D levels were not significantly different between the two groups. Bioavailable 25(OH)D was significantly decreased in PTL women (p= .011), and VDBP was significantly increased in PTL women (p= .004) compared to the controls. Bioavailable 25(OH)D was lower in women with GT/TG and TT rs7041 genotypes than in those with GG, with statistical significance in women with the TT allele (p= .048). VDBP was higher in women with GT/TG and TT than those with GG, but there was no statistical significance. In PTL prevalence, bioavailable 25(OH)D and VDBP, the odds ratio increased by 1.463 times in GT/TG (p= .728) and increased by 1.675 times in TT compared to the GG allele (p= .640). In receiver operating characteristic (ROC) analysis for bioavailable 25(OH)D and VDBP, the AUC was 0.665 and 0685, respectively. The optimum cutoff of bioavailable 25(OH)D and VDBP levels for the diagnosis of PTL was calculated as 0.6 ng/mL and 523 µg/mL, respectively.
Conclusions: Pregnant women with the VDBP rs7041(c.1296 T > G) T allele genotype had reduced serum levels of bioavailable 25(OH)D and were more likely to develop PTL. Therefore, if the T allele is found in the VDBP rs7041 SNP genotyping test before or during pregnancy, more careful prenatal care may be required because of the increased risk of PTL.
Keywords: Vitamin D; maternal adverse outcome; pregnancy; preterm labor; single nucleotide polymorphism; vitamin D-binding protein.