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

Abstract

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.

Vitamin D Status, VDR, and TLR Polymorphisms and Pulmonary Tuberculosis Epidemiology in Kazakhstan

“…Much of the research work focused on the four main SNPs—FokI, TaqI, ApaI, and BsmI. The association of these SNPs was tested for various health conditions in many populations, including TB [ 57 , 58 , 59 , 60 ]. To date, a single research report has been published on the association of VDR polymorphisms with susceptibility to TB in the Kazakh population.…”

Exploring Gene–Diet Interactions for Mother–Child Health: A Systematic Review of Epidemiological Studies

“…Recent research offers evidence that maternal VDR gene polymorphisms likely play a pivotal role by influencing the biological activity of vitamin D in certain unfavorable pregnancy outcomes [62,63]. The VDR gene encodes the vitamin D3 receptor, which belongs to the nuclear hormone receptor superfamily and plays a pivotal role in mediating the biological effects of vitamin D [74].…”

“…The increasing prevalence of HDP is a significant factor contributing to almost 20% of worldwide maternal mortality, elevating the associated risks for maternal, child, and long-term cardiovascular health [59][60][61]. The existing research has predominantly focused on exploring the relationship between vitamin D status, gene variations in the vitamin D metabolic pathway, and HDP, frequently neglecting possible interactions among these factors [62,63]. For instance, Si and colleagues investigated the interplay between maternal SNPs in genes related to the vitamin D metabolic pathway (GC, CYP24A1, CYP3A4, CYP27B1, LRP2, and VDR) and vitamin D levels during pregnancy, examining their impact on gestational blood pressure and HDP development.…”