Vitamin D and Pregnancy: Unraveling VDR Gene's Role in Hypertensive Disorders, study finds

Investigating genetic variations in the vitamin D receptor (VDR) gene has revealed inconsistent associations with hypertensive disorders of pregnancy (HDP) across diverse populations. Recently published systematic review focuses on assessing laboratory protocols for VDR gene variant detection and their relationships to HDP. Hypertensive disorders, which include gestational hypertension and preeclampsia, pose significant risks for maternal and infant health. Emerging evidence suggests that vitamin D insufficiency is prevalent in women experiencing HDP, highlighting the importance of vitamin D's role in various biological processes during pregnancy.

Polymorphisms in the VDR Gene

The VDR gene, located on chromosome 12, has several polymorphisms, notably FokI, BsmI, ApaI, and TaqI. These variations have been associated with altered VDR functionality and may disrupt molecular pathways critical to vascular and immune health, thereby increasing susceptibility to HDP. Specifically, the loss of function associated with these polymorphisms may lead to endothelial dysfunction and an imbalance in the renin-angiotensin-aldosterone system, influencing maternal blood pressure.

Review Methodology and Study Selection

The review systematically searched databases such as PubMed and Scopus, yielding 170 candidate articles, ultimately culminating in the inclusion of nine studies. The majority (67%) of the studies originated from Asia, with others from Europe and Latin America, primarily employing case-control designs. A range of laboratory methods for detecting VDR variants was documented, with PCR-restriction fragment length polymorphism (PCR-RFLP) being the most common. Results indicated that associations with VDR variants were ascribed variably, with FokI presenting a significant relationship with HDP in most Asian studies.

Variability in Study Findings

Notably, two studies utilizing TaqMan PCR found associations with the FokI variant while an AS-PCR method for the ApaI variant showed no link in a Pakistani population, underscoring the variability in findings due to methodological differences. Additionally, while some studies reported BsmI's relation to HDP, other populations showed no significant associations.

Implications and Future Directions

The inconsistent data may stem from variant detection protocols and contextual factors such as environmental influences and lifestyle, emphasizing the necessity for standardized protocols across studies to improve the reliability of genetic association findings. Strengthening VDR detection methods can enhance precision in individual patient management and public health strategies aimed at minimizing HDP risks, advocating for tailored vitamin D supplementation approaches. Future research should emphasize haplotype analyses and broadening case-control studies to confirm these genetic associations comprehensively.

Key Points

- Investigated genetic variations in the vitamin D receptor (VDR) gene reveal inconsistent relationships with hypertensive disorders of pregnancy (HDP), which include gestational hypertension and preeclampsia, underscoring the significance of vitamin D in maternal and infant health.

- The VDR gene, located on chromosome 12, has several significant polymorphisms like FokI, BsmI, ApaI, and TaqI, which may disrupt molecular pathways related to vascular and immune health, potentially leading to increased susceptibility to HDP through mechanisms such as endothelial dysfunction and disturbances in the renin-angiotensin-aldosterone system.

- A systematic review employed databases like PubMed and Scopus, filtering down from 170 candidate articles to include nine studies, predominantly derived from Asian populations (67%). The studies primarily utilized case-control design with PCR-restriction fragment length polymorphism (PCR-RFLP) recognized as the most common laboratory method for detecting VDR variants.

- Variability in study findings was noted, with specific methodologies yielding different results; for instance, while associations between the FokI variant and HDP were identified in most Asian studies, results with TaqI and ApaI variants differed, demonstrating how methodological differences can affect outcomes.

- Inconsistent associations with VDR variants could result from variable detection protocols, environmental influences, and lifestyle factors, necessitating standardized methodologies to enhance the reliability of genetic epidemiology findings in relation to hypertensive disorders.

- Recommendations for future research include focusing on haplotype analyses and expanding case-control studies to solidify the understanding of genetic associations, as well as improving VDR detection methods to inform personalized patient care and public health strategies aimed at reducing the risks of HDP through tailored vitamin D supplementation.

Reference –

Yakubu Ibrahim et al. (2025). A Plethora Of Laboratory Protocols For Vitamin D Receptor (VDR) Gene Variants Detection: A Systematic Review Of Associations With Hypertensive Disorders Of Pregnancy. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07510-6.