Association between Vitamin D receptor (VDR) gene polymorphisms and hypertensive disorders of pregnancy: a systematic review and meta-analysis

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are currently one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Recent studies provide evidence that maternal Vitamin D receptor (VDR) gene polymorphisms probably play a key role by affecting the biological function of vitamin D in some adverse pregnancy outcomes, while the relationship between the VDR gene polymorphisms and the risk of HDP remains controversial in current studies. This systematic review and meta-analysis aimed to comprehensively evaluate the association of the VDR gene polymorphisms with HDP susceptibility. METHODS: This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and a protocol has been registered in the PROSPERO (ID: CRD42022344383) before commencing this review. PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until January 21, 2023. Case-control and cohort studies that reported the association of the VDR gene polymorphisms with HDP were included. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for non-randomized studies. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of the five models (allele model, dominant model, recessive model, homozygous model, heterozygous model) were pooled respectively, and subgroup analysis was performed based on ethnicity. RESULTS: A total of ten studies were included. The VDR gene ApaI polymorphism was associated with HDP susceptibility in the dominant model (OR: 1.38; 95% CI [1.07–1.79]; P = 0.014) and the heterozygote model (OR: 1.48; 95% CI [1.12–1.95]; P = 0.006). In subgroup analysis, the heterozygote model (OR: 2.06; 95% CI [1.21–3.52]; P = 0.008) of the ApaI polymorphism was associated with HDP in Asians, but not in Caucasians. CONCLUSION: The VDR gene ApaI polymorphism may be associated with HDP susceptibility. Insufficient evidence to support the existence of ethnic differences in this association.