Association between the rs2228570 polymorphism of the Vitamin D Receptor gene and serum vitamin D levels: A systematic review and meta-analysis.

Vitamin D deficiency is a widespread condition across the world. The rs2228570 (FokI) polymorphism in the vitamin D receptor (VDR) gene has been associated with vitamin D-related diseases, but its influence on circulating 25(OH)D levels remains unclear. This systematic review and meta-analysis aimed to assess the association between the rs2228570 polymorphism and serum 25(OH)D. The search was conducted in PubMed, Scopus, and Cochrane databases. Eligible studies included healthy adults with available genotyping of the VDR gene, and measurement of 25(OH)D. The exclusion criteria included pregnant or lactating women, obese participants, and individuals receiving supplements. Of the 66 articles that met the inclusion criteria, 45 were included in the meta-analysis, representing 15,256 participants mainly from Europe, Asia and America. The included studies were both case-control and cross-sectional, and study quality was assessed using standardized tools. No significant associations were observed in any of the genetic models analyzed (CC vs TT, CT vs TT, (CC+CT) vs TT, or (TT+CT) vs CC). Subgroup analyses by continent showed no significant associations (p>0.05), except for the American subgroup for the CT vs TT comparison (p=0.04). In Fair-quality studies, higher 25(OH)D levels were observed among C-allele carriers, although these findings were accompanied by substantial heterogeneity across comparisons (I² range: 81.4% to 95.1%). This meta-analysis found no evidence that the rs2228570 (FokI) polymorphism influences circulating 25(OH)D. These results contribute to delineate the limited influence of the FokI polymorphism in 25(OH)D levels and support the need for future studies integrating environmental and functional factors.