Serum vitamin D-binding protein (VDBP) concentration and rs7041 genotype may be associated with preterm labor

Abstract

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
• vitamin D-binding protein
• single nucleotide polymorphism
• pregnancy
• maternal adverse outcome
• preterm labor

Acknowledgements

Ethics approval: This study was approved by the Institutional Review Board of Gyeongsang National University Hospital (IRB No. GNUH 2017-01-004).

Consent to participate: All of the subjects included in this study were informed in writing that their sensitive private information would not be disclosed to third parties, and all patients provided informed consent for the use of their clinical data for research purposes.

Authors contributions

Min-Chul Cho and In Ae Cho: protocol development, data collection, and management, and manuscript writing/editing; Hyun Kyoung Seo, Min Ji Kang, Jae Yoon Jo, Jeong Kyu Shin, and Soon Ae Lee: data collection and management; Seung Chan Kim and Rock-Bum Kim: protocol development and statistical analysis of data; and Won Jun Choi: protocol development, data analysis, and manuscript writing/editing.

Disclosure statement

The authors declare that they have no conflicts of interest relevant to this study.

Data  availability statement

The data used to support the findings of this study are available from the corresponding author upon request.

Additional information

Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education [2020R1I1A3067635].