Department of Medical Services, Zhengzhou Central Hospital affiliated to Zhengzhou University, Zhengzhou 450001, China.
Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.
Gene. 2018 Dec 15;678:361-369. doi: 10.1016/j.gene.2018.08.056. Epub 2018 Aug 16.
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.
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.
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.
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.
CYP2R1 是维生素 D 代谢途径中的关键基因。有研究表明，欧洲人群 CYP2R1 基因变异与 25（OH）D 浓度有关，25（OH）D 是外周血中维生素 D 水平和状态的生物标志物。然而，尚未进行过包括不同种族在内的该影响的综合荟萃分析。本荟萃分析的目的是评估 CYP2R1 基因变异与 25（OH）D 水平和维生素 D 状态之间的关系。
系统检索了 PubMed、EMBASE、Web of Science、CNKI 和万方数据库，截至 2018 年 5 月。报告遵循 PRISMA 指南。使用 STREGA 系统评估证据质量。随机或固定效应模型合并估计值，并进行亚组检验以评估种族差异。I ² 统计量用于量化由于异质性引起的研究间变异。
符合纳入标准的 16 篇文章共有 52417 名参与者，纳入荟萃分析。对于 rs10741657，与 AA 基因型相比，GG 基因型与 25（OH）D 水平呈明显下降趋势[SMD=−2.32，95%CI（−4.42，−0.20）；SMD=−3.46，95%CI（−6.60，−0.33）和 SMD=−0.24，95%CI（−0.51，−0.03），用于总人群、白种人和亚洲人群，分别具有以下异质性 I²=37.9%、69.2%和 24.5%]。然而，在 AG/AA 遗传模型下，25（OH）D 水平的显著变化[SMD 和 95%CI：−1.27（−2.32，−0.23）]仅在白种人群中明显。荟萃分析表明，维生素 D 缺乏症的风险等位基因 G 与维生素 D 缺乏症的风险增加相关（OR=1.09；95%CI=1.03-1.15，P=0.002）。rs10741657 与维生素 D 缺乏症风险增加的关联在显性模型（GG+AG/AA）下显著（OR=1.42；95%CI=1.11-1.83，P=0.006），但在隐性模型（GG/AG+AA）下不显著（OR=1.28；95%CI=0.89-1.84，P=0.181）。没有证据表明存在发表偏倚。
已发表的文章提供了证据，支持 CYP2R1 基因的 rs10741657 多态性在决定 25（OH）D 水平和维生素 D 缺乏症的存在方面起着重要作用。
