维生素D受体基因多态性与维生素D缺乏性佝偻病遗传关联性Meta分析  

Assoiation between polymorphisms of vitamin D receptor gene and vitamin D deficiency rickets:a meta-analysis

作　　者：李卫国[1] 刘丽君[1] 李湘津[1] 周晓菊[1] 杨慧[1] 李宇宁[1] 

机构地区：[1]兰州大学第一医院儿科,兰州730000

出　　处：《中国循证儿科杂志》2011年第4期264-274,共11页Chinese Journal of Evidence Based Pediatrics

基　　金：甘肃省科技厅科技攻关项目:GS012-A43-090;兰州市科技局科研基金项目:2009-1-51

摘　　要：目的评价维生素D受体（VDR）基因多态性与维生素D缺乏性佝偻病（佝偻病）的遗传关联性。方法制定原始文献的纳入标准及检索策略,检索PubMed、Springer、Science Direct、Web of Science、中国期刊全文数据库、维普中文科技期刊数据库和万方数据库,收集VDR基因FokⅠ、ApaⅠ、BsmⅠ和TaqⅠ位点多态性与佝偻病相关性的病例对照研究,以佝偻病患儿为病例组。依据NHI-NHGRI研究工作组2007年制定的遗传关联性研究报告规范为基础,并依据相关文献选取其中的14条标准用于评价文献偏倚。以基因型频率为指标,提取数据后先确定最佳遗传模型,采用Stata 11.0软件进行Meta分析,计算合并的OR值及其95%CI。结果 19篇病例对照研究进入Meta分析。①FokⅠ位点采用共显性模型（FF基因型vsff基因型;FF基因型vsFf基因型）分析,病例组704例,对照组596例。Meta分析结果显示,亚洲人群FF基因型较ff基因型（OR=4.59,95%CI：2.98~7.07）和Ff基因型（OR=2.58,95%CI：1.79~3.73）患佝偻病的风险显著增加;高加索人群FokⅠ位点与佝偻病无显著关联性（FF基因型vsff基因型,OR=2.50,95%CI：0.76~8.19;FF基因型vsFf基因型,OR=1.18,95%CI：0.66~2.10）;非洲人群FF基因型较ff基因型患佝偻病的风险显著增加（OR=5.81,95%CI：1.21~27.98）。②ApaⅠ位点采用显性模型（AA＋Aa基因型vsaa基因型）分析,病例组338例,对照组459例。亚洲人群和非洲人群ApaⅠ位点与佝偻病均无显著关联性,OR分别为1.04（95%CI：0.72~1.49）和0.98（95%CI：0.57~1.71）;高加索人群AA＋Aa基因型患佝偻病的风险增高（OR=5.50,95%CI：1.22~24.75）。③BsmⅠ位点采用显性模型（bb基因型vsBb＋BB基因型）分析,病例组822例,对照组736例。亚洲人群BsmⅠ位点bb基因型较Bb＋BB基因型患佝偻病的风险降低（OR=0.46,95%CI：0.23~0.92）,非洲人群BsmⅠ位点与佝偻病无显著关联性（OR=1.65,95%CI：0.95~2.88）。④TaqⅠ�Objective To evaluate the association between vitamin D receptor（VDR） gene polymorphsims and nutritional vitamin D deficiency rickets.Methods PubMed,Springer,Science Direct,Web of Science,China National Knowledge Infrastructure,VIP Chinese Periodical Database and Wanfang Chinese Periodical Database were searched for the case-control study on the association of VDR gene polymorphisms with rickets（up to February 2011）.Meta-analysis of all the eligible studies was performed,which focused on four most commonly investigated VDR polymorphisms： FokⅠ,ApaⅠ,BsmⅠ and TaqⅠ.The best genetic model in pooled analyses was selected.Stata 11.0 software was applied for investigating the heterogeneity among individual studies and the pooled odds ratio（OR） and 95% confidence interval（CI） were calculated.Sensitivity analyses were performed by excluding studies with controls inconsistent with Hardy-Weinberg equilibrium.Results A total of 19 eligible studies were included.①Codominant genetic model was used to analyze the FokⅠ single nucleotide polymorphisms（SNPs）.There was no heterogeneity among included studies.Subgroup analyses showed that FokⅠ SNP was significantly associated with rickets（FF vs ff： OR=4.59,95%CI：2.98-7.07;FF vs Ff：OR=2.58,95%CI：1.79-3.73） in Asian population.However,the association was not significant in Caucasian population（FF vs ff：OR=2.50,95%CI：0.76-8.19;FF vs Ff： OR=1.18,95%CI：0.66-2.10）.②Dominant genetic model of A allele（AA＋Aa vs aa）was used to analyze ApaⅠ SNP.There was no significant heterogeneity among included studies.No significant association between ApaⅠ SNP and rickets was found in Asian population（OR=1.04,95%CI： 0.72-1.49） and Africans（OR=0.98,95%CI： 0.57-1.71）.But in Caucasian population,a study suggested that aa genotype was a protective factor for rickets（AA＋Aa vs aa,OR=5.50,95%CI： 1.22-24.75）.③Dominant genetic model of B allele（bb vs Bb＋BB） was used to analyze BsmⅠ SNP.Meta-analysis showed that the

关 键 词：维生素D受体 佝偻病 基因多态性 META分析 

分 类 号：R723[医药卫生—儿科]