Cao Yan, Wang Xinjing, Cao Zhihong, Cheng Xiaoxing
Key Laboratory of Tuberculosis Prevention and Treatment, and Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis, The 309th Hospital Beijing 100091, China.
Int J Clin Exp Med. 2015 Jun 15;8(6):10187-203. eCollection 2015.
Vitamin D receptor (VDR) is a receptor of vitamin D3, which plays a pivotal role in regulating cell proliferation and differentiation, lymphocyte activation and cytokine production, and is associated with TB susceptibility. Growing studies explored the association of TaqI polymorphism of VDR with tuberculosis (TB) susceptibility. However, the results were inconsistent and conflicting. To assess the relationship between the VDR TaqI gene polymorphism and the risk of TB, a meta-analysis was performed. Databases including PubMed and EMbase were systematically searched for genetic association studies of TaqI polymorphism of VDR and tuberculosis until February 15, 2015. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the strength of the association between VDR TaqI gene polymorphism and TB risk, meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Thirty-eight studies with a total of 6881 cases and 7511 controls were reviewed in the present meta-analysis. A statistically significant correlations were observed between VDR TaqI gene polymorphism and TB risk in South and West Asians (t vs. T: OR=1.27, 95% CI=1.07-1.51, P=0.007; tt vs. TT: OR=1.59, 95% CI=1.11-2.26, P=0.011; tt vs. Tt + TT: OR=1.43, 95% CI=1.17-1.73, P=0.000; tt + Tt vs. TT: OR=1.32, 95% CI=1.05-1.67, P=0.019). Heterogeneity between studies was not pronounced, and meta-regression found no source contributed to heterogeneity. However, after stratified analysis with respect to genotyping methods and sample size, significant association was found in "small" studies (<500 participants) and studies with "PCR-RFLP" methods. Synthesis of the available studies suggests that t allele of the VDR TaqI polymorphism is significantly associated with an increased TB risk in South and West Asians.
维生素D受体(VDR)是维生素D3的受体,在调节细胞增殖与分化、淋巴细胞活化及细胞因子产生中起关键作用,且与结核病易感性相关。越来越多的研究探讨了VDR的TaqI多态性与结核病(TB)易感性的关联。然而,结果并不一致且相互矛盾。为评估VDR TaqI基因多态性与TB风险之间的关系,进行了一项荟萃分析。系统检索了包括PubMed和EMbase在内的数据库,查找截至2015年2月15日关于VDR的TaqI多态性与结核病的基因关联研究。由两名独立作者提取数据,并计算合并比值比(OR)及95%置信区间(CI)以评估VDR TaqI基因多态性与TB风险之间关联的强度,进行了元回归和亚组分析以确定异质性来源。本荟萃分析纳入了38项研究,共6881例病例和7511例对照。在南亚和西亚人群中,观察到VDR TaqI基因多态性与TB风险之间存在统计学显著相关性(t与T:OR = 1.27,95% CI = 1.07 - 1.51,P = 0.007;tt与TT:OR = 1.59,95% CI = 1.11 - 2.26,P = 0.011;tt与Tt + TT:OR = 1.43,95% CI = 1.17 - 1.73,P = 0.000;tt + Tt与TT:OR = 1.32,95% CI = 1.05 - 1.67,P = 0.019)。研究之间的异质性不明显,元回归未发现导致异质性的来源。然而,在按基因分型方法和样本量进行分层分析后,在“小”研究(<500名参与者)和采用“PCR-RFLP”方法的研究中发现了显著关联。现有研究的综合分析表明,VDR TaqI多态性的t等位基因与南亚和西亚人群中TB风险增加显著相关。