Association of vitamin D and gene variants in the vitamin D metabolic pathway with preterm birth

Abstract

Objectives: The aim of this study was to explore the association of vitamin D (VitD) levels during pregnancy and its metabolic pathway genes with the risk for preterm birth (PTB) among pregnant women in southeast China.

Methods: This study was conducted in Zhoushan Maternal and Child Health Hospital, Zhejiang, from August 2011 to May 2018. Plasma 25-hydroxyvitamin vitamin D [25(OH)D] levels in three trimesters and single-nucleotide morphisms in the VitD metabolic pathway were measured. Relevant information was collected using questionnaires and an electronic medical recorder system. Multiple statistical methods including linear regression, logistic regression, and crossover analysis were applied.

Results: The prospective cohort study included 3465 pregnant women, of which 202 were PTB (week of gestation at delivery: 33.38 ± 4.05), accounting for 5.8%. After adjusting for potential confounders, VitD sufficiency (≥30 ng/mL) in the second and third trimesters was associated with longer gestational age at delivery compared with VitD deficiency (<20 ng/mL). However, no significant association was found between VitD with the risk for PTB. rs7041, rs10210408, and rs2228171 were associated with gestational week and the risk for PTB. Significant associations were found of rs10210408, rs2209314, rs1155563, rs2544381 and the status of VitD in the second and third trimester with the gestational week. We also found that rs7041 and VitD in the second trimester might exert interaction on gestational week and the risk for PTB (P_inter = 0.038; P_inter = 0.019); rs16846876 and VitD in the second trimester might exert interaction on gestational week (P_inter = 0.024); rs4334089 and VitD in the third trimester might exert interaction on gestational week (P_inter = 0.024). Similar results were found when we tested pregnant women's plasma 25(OH)D in the first and second trimesters.

Conclusions: Women with VitD deficiency were associated with shorter gestational weeks. Single-nucleotide morphisms in VitD metabolic pathway genes were significantly associated with gestation week and the risk for PTB, mainly in vitamin D-binding protein (GC) and low-density lipoprotein-related protein 2 (LRP2)genes. Additionally, maternal VitD with GC gene and maternal VitD with vitamin D receptor (VDR) gene might exert interactions on the risk for PTB.

Keywords: 25(OH)D; Preterm birth; Vitamin D; Vitamin D metabolic pathway.