A receptor is a structure typically located within a cell membrane that receives and communicates information according to a unique chemical signal. The vitamin D receptor (VDR) is located on many cell types within the human body and mediates signals from calcitriol, a form of vitamin D. The relative abundance of VDRs within the body may be due to the many important roles that vitamin D plays in human health.

VDRs have been described in research to play a role in both innate and adaptive immune responses. The reduced function of VDRs has been linked to several systemic diseases and certain autoimmune disorders. Environmental and genetic factors are believed to regulate VDR function.

A recently published systematic review and meta-analysis published by Usategui-Martín and colleagues explored the impact of VDR gene polymorphisms on the absorption of vitamin D supplementation. Polymorphisms occur when there are multiple variations or possibilities of a trait or characteristic for one gene. A common example of a gene polymorphism is the ABO blood group system in humans and other primates.

As opposed to ABO blood typing, there have been more than 900 variants of VDR reported. Some well-researched variants of VDRs include Taql (rs731236), Fokl (rs10735810), Apal (rs7975232), and BsmI (rs1544410). Although the ApaI and BsmI variants showed no significant changes in VDR response to vitamin D supplementation, TaqI and certain genotypes of the FokI variant indicated a better response from VDRs in the presence of supplementation with vitamin D.

The FokI VDR variant is a polymorphism that has been associated with a predisposition to certain systemic illnesses including type 2 diabetes mellitus. However, the study by Usategui-Martín and colleagues indicated that the FF allele, or variant, may be associated with greater VDR activity. The FF genotype has also been associated with higher bone mineral density, reduced risk of certain bone fractures, and better calcium absorption.

The TaqI polymorphism has been linked to an increase in messenger RNA stability. Study results published by Usategui-Martín and colleagues indicate that the TaqI polymorphism may be associated with a better response to supplementation with vitamin D.

The authors of this study reported some limitations to the meta-analysis that include small sample sizes. In addition, most of the research included in the study by Usategui-Martín and colleagues did not take sunlight exposure into account. Sunlight exposure is an environmental factor important to the modulation of VDRs.

The study by Usategui-Martín and colleagues suggested that certain gene variants of VDRs may respond to vitamin D supplementation differently. Future research may further elucidate the connection between genetic and environmental factors and vitamin D receptor function.

By Colleen Ambrose, ND, MAT