Effects of CYP2R1 Gene Variants on Vitamin D Levels and Status: A Systematic Review and Meta-analysis

Background And Objective: CYP2R1 is a key gene in the vitamin D metabolic pathway. It has been suggested that CYP2R1 gene variants in European populations are associated with concentrations of 25(OH)D, a biomarker of vitamin D levels and status in peripheral blood. However, a comprehensive meta-analysis of this effect including different ethnicities has never been conducted. The objective of this meta-analysis was to evaluate the association between CYP2R1 gene variants and 25(OH)D levels and vitamin D status.

Methods: PubMed, EMBASE, Web of Science, CNKI and Wanfang databases were systematically searched up to May 2018. Reporting followed PRISMA guidelines. The quality of the evidence was assessed using the STREGA system. Random or fixed effects model combined estimates and sub-group tested for ethnic differences. The I statistic quantified between-study variation due to heterogeneity.

Results: Sixteen articles with a total of 52,417 participants met the inclusion criteria and were included in the meta-analysis. For rs10741657, GG genotype was associated with a clear descending trend of 25(OH)D levels when compared with the AA genotype [SMD = -2.32, 95% CI (-4.42, -0.20); SMD = -3.46, 95% CI (-6.60, -0.33) and SMD = -0.24, 95% CI (-0.51, -0.03) for total, Caucasian and Asian groups, respectively] with the following heterogeneities I = 37.9%, 69.2% and 24.5%, respectively. However, under the AG/AA genetic model, significant changes in 25(OH)D levels [SMD and 95% CI: -1.27(-2.32, -0.23)] were only evident in the Caucasian population. The meta-analysis on vitamin D deficiency showed that the risk-allele G was associated with an increased risk of vitamin D deficiency (OR = 1.09; 95% CI = 1.03-1.15, P = 0.002). The association between rs10741657 and increased risk of vitamin D deficiency was significant (OR = 1.42; 95% CI = 1.11-1.83, P = 0.006) under the dominant model (GG + AG/AA), but not under the recessive model (GG/AG + AA), (OR = 1.28; 95% CI = 0.89-1.84, P = 0.181). There was no evidence of publication bias.

Conclusion: Published articles provide evidence supporting a major role for the rs10741657 polymorphism of the CYP2R1 gene in determining 25(OH)D levels and the presence of vitamin D deficiency.