A plethora of laboratory protocols for vitamin D receptor (VDR) gene variants detection: a systematic review of associations with hypertensive disorders of pregnancy

Abstract

Introduction: Hypertensive disorders of pregnancy constitute the major cause of maternal morbidity and mortality. Genetic variation involving VDR gene variants was thought to play a significant role in aetiopathogenesis of HDP. Vitamin D receptor (VDR) gene polymorphisms are thought to be implicated in the development of hypertensive disorders of pregnancy (HDP). However, the association of the variants with HDP is inconsistently reported. The study aims to review the laboratory protocols of VDR variant detection and association with HDP. Methods This study involved one or more of the major VDR gene variants (FokI, BsmI, ApaI, and TaqI) in HDP. The Web of Science, PubMed, Scopus, MEDLINE and CINAHL databases were searched for articles. Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) was used. The study was registered in the PROSPERO database (registration number CRD42022362561). Results Our analysis of VDR variant detection protocols revealed that approximately 6 (67%) studies used polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), of which 3 (33%) reported a significant association with the FokI variant. Two (22%) of the studies used TaqMan PCR and found an association with the FokI variant. Only 1 (11%) study utilized allele-specific PCR (AS-PCR) to genotype the ApaI variant. Based on the analysis of the variants with populations, 4 studies (44%) reported an association with the FokI variant in Asians. Two studies (22%) reported that the BsmI variant is common among Caucasians. Conclusions The detection protocols evaluated were found to be sensitive in detecting some variants in certain populations but not in others, however, the variants were found to be population-specific. Our findings could potentially be useful in stimulating the discovery of distinct biomarkers specific to various populations and could as well prompt the personalised management of hypertension in pregnancy.