The Association of Vitamin D and Its Pathway Genes’ Polymorphisms with Hypertensive Disorders of Pregnancy: A Prospective Cohort Study

Objective: We aimed to explore the effect of single nucleotide polymorphism (SNP) in the genes of the vitamin D (VitD) metabolic pathway and its interaction with VitD level during pregnancy on the development of hypertensive disorders of pregnancy (HDP). Methods: The study was conducted in the Zhoushan Maternal and Child Health Care Hospital, China, from August 2011 to May 2018. The SNPs in VitD metabolic pathway-related genes were genotyped. Plasma 25-hydroxyvitamin vitamin D (25(OH)D) levels was measured at first (T1), second (T2), and third (T3) trimesters. The information of systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the diagnosis of HDP were extracted from the electronic medical record system. Multivariable linear and logistic regression models and crossover analysis were applied. Results: The prospective cohort study included 3699 pregnant women, of which 105 (2.85%) were diagnosed with HDP. After adjusting for potential confounders, VitD deficiency at T2, as well as the change of 25(OH)D level between T1 and T2, were negatively associated with DBP at T2 and T3, but not HDP. Polymorphisms in CYP24A1, GC, and LRP2 genes were associated with blood pressure and HDP. In addition, VitD interacted with CYP24A1, GC, and VDR genes’ polymorphisms on blood pressure. Furthermore, participants with polymorphisms in CYP24A1-rs2248137, LRP2-rs2389557, and LRP2-rs4667591 and who had VitD deficiency at T2 showed an increased risk of HDP. Conclusions: The individual and interactive association between VitD deficiency during pregnancy and SNPs in the genes of the VitD metabolic pathway on blood pressure and HDP were identified.