Genetic variations of vitamin D receptor and vitamin D supplementation interaction in relation to serum vitamin D and metabolic traits: a systematic review and meta-analysis.

Background: It is now becoming increasingly recognized that the effects of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity, and/or the presence of genetic variants, which affect individual responses to supplementation. This study investigates the interaction between metabolic traits and circulating 25-hydroxyvitamin-D (25OHD) concentration with 4 polymorphisms of vitamin D receptor (VDR) including BsmI, ApaI, TaqI, FokI, and vitamin D supplementation. Methods: A systematic review and meta-analysis of papers until August 2021 on PubMed, The Cochrane Library, Scopus, Web of Science, Google Scholar, ProQuest, Science Direct, and Embase about the association between functionally relevant VDR variants and vitamin D supplementation on circulating 25OHD and metabolic traits. Results: A total of 2994 cases from 16 randomized controlled trial (RCT) studies were included in meta-analyses. There were no significant changes in the serum concentrations of 25OHD and metabolic traits after vitamin D supplementation in different variants of BsmI, ApaI, TaqI, and FokI polymorphism in the VDR gene in the overall analysis (p>0.05). However, the results showed there is significant interaction between these above VDR polymorphisms and vitamin D supplement on serum 25OHD level after subgroup analyses based on the study duration, gender, age, BMI, health status, Hardy-Weinberg Equilibrium, PCR, and race (p<0.05). Conclusions: The present meta-analysis demonstrates that the effect of vitamin D supplementation on serum 25OHD and metabolic traits is independent of genetic variants of the VDR gene (BsmI, ApaI, TaqI, and FokI). However, future trials should consider inter-individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of metabolic health.