ACE基因插入/缺失多态性与骨性关节炎关联性的Meta分析和试验序贯分析  

Association between the insertion/deletion polymorphism of ACE gene and osteoarthritis: a meta-analysis and trial sequential analysis

作　　者：陈磊[1,2] 艾金伟 兰姗[1] 唐玲玲[1] 吴文凤[1] 裴斌[1,2] CHEN Lei AI Jinwei LAN Shan TANG Lingling WU Wenfeng PEI Bin(Evidence-Based Medicine Center, Xiangyang No.1 people＇s Hospital, Hubei University of Medicine, Xiangyang, 441000, P.R.China Department of Orthopaedics, Xiangyang No.1 People＇s Hospital, Hubei University of Medicine, Xiangyang, 441000, P.R.China)

机构地区：[1]湖北医药学院附属襄阳市第一医院循证医学中心,湖北襄阳441000 [2]湖北医药学院附属襄阳市第一人民医院骨科,湖北襄阳441000

出　　处：《中国循证医学杂志》2017年第2期135-143,共9页Chinese Journal of Evidence-based Medicine

基　　金：湖北省卫生计生西医类2015-2016年度一般项目(编号:WJ2015MB187);湖北医药学院教研重点项目(编号:2015025);襄阳市科技计划项目(编号:2010GG3A21)

摘　　要：目的通过Meta分析和试验序贯分析(TSA)系统评价血管紧张素Ⅰ转换酶(ACE)基因插入/缺失(I/D)多态性与骨性关节炎(OA)患病风险之间的关联性。方法计算机检索Pub Med、EMbase、CNKI、CBM、VIP和Wan Fang Data数据库,搜集ACE基因I/D多态性与OA发病风险关联性的病例-对照研究或队列研究,检索时间均为建库至2016年10月12日。由2位评价者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata 13.1软件进行Meta分析,运用TSA v0.9软件进行试验序贯分析(TSA)。结果纳入6个病例-对照研究,合计1 165例OA患者和1 029例健康对照。Meta分析结果显示,ACE基因I/D多态性与OA患病风险存在关联性[DD+DI vs.II:OR=1.72,95%CI(1.02,2.90),P=0.04;DI vs.II:OR=1.65,95%CI(1.06,2.56),P=0.03]。按种族进行亚组分析,结果显示:在高加索人种中,ACE基因I/D多态性与OA患病风险存在关联性[DD vs.DI+II:OR=2.10,95%CI(1.54,2.85),P<0.01;DD+DI vs.II:OR=3.11,95%CI(2.20,4.39),P<0.01;DD vs.II:OR=4.01,95%CI(2.68,6.00),P<0.01;DI vs.II:OR=2.65,95%CI(1.45,4.87),P<0.01;D vs.I:OR=2.11,95%CI(1.72,2.58),P<0.01];TSA结果显示累积Z值均跨过了传统界值和TSA界值,说明ACE基因I/D多态性与高加索人种OA患病风险关联性Meta分析结果是可靠的。在亚洲人种中,ACE基因I/D多态性与OA患病风险不存在关联性[DD vs.DI+II:OR=0.80,95%CI(0.60,1.07),P=0.13;DD+DI vs.II:OR=1.08,95%CI(0.87,1.35),P=0.49;DD vs.II:OR=0.86,95%CI(0.62,1.20),P=0.38;DI vs.II:OR=1.18,95%CI(0.93,1.50),P=0.19;D vs.I:OR=0.93,95%CI(0.83,1.14),P=0.73],TSA结果显示除DD vs.DI+II遗传模型外,其余遗传模型累积Z值均未跨过TSA界值和期望信息量(RIS),提示样本量不足。结论当前证据显示ACE D等位基因是高加索人种OA的危险因素,但ACE基因I/D多态性是否与亚洲人种OA存在关联性,尚需更多试验予以明确。Objective To systematically review the association between angiotension-converting enzyme （ACE） gene insertion/deletion （I/D） polymorphism and osteoarthritis （OA） by using meta-analysis and trial sequential analysis （TSA）. Methods The PubMed, EMbase, CNKI, CBM, VIP, and WanFang Data were searched up to October 12th, 2016 for case-contrcl or cohort studies on the correlation between ACE I/D polymorphism and OA risk. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis and TSA analysis were performed using Stata 13.1 software and TSA v0.9 soft ware. Results A total of six case-control studies involving 1 165 OA patients and 1 029 controls were included. The results of meta-analysis showed that the ACE I/D was associated with OA risk （DD＋DI vs. II： OR=1.72, 95%CI 1.02 to 2.90, P=0.04; DI vs. II： OR=1.65, 95%CI 1.06 to 2.56, P=0.03）. Subgroup analysis of ethnicity showed that, in Caucasians, the ACE I/D was associated with OA risk （DD vs. DI＋II： OR=2.10, 95%CI 1.54 to 2.85, P〈0.01; DD＋DI vs. II： OR=3.11, 95%CI 2.20 to 4.39, P〈0.01; DD vs. II： OR=4.01, 95%CI 2.68 to 6.00, P〈0.01; DI vs. II： OR=2.65, 95%CI 1.06 to 2.56, P〈0.01; D vs. I： OR=2.11, 95%CI 1.72 to 2.58, P=0.73）. And TSA showed that all of the cumulative Z-curve strode the conventional and TSA threshold value which suggested the result of the association between ACE I/D polymorphism and OA in Caucasians was very reliable. However, the association did not exist in Asians （DD vs. DI＋II： OR=0.80, 95%CI 0.60 to 1.07, P=0.13; DD＋DI vs. II： OR=1.08, 95%CI 0.87 to 1.35, P=0.49; DD vs. II： OR=0.86, 95%CI 0.62 to 1.20, P=0.38; DI vs. II： OR=1.18, 95%CI 0.93 to 1.50, P=0.19; D vs. I： OR=0.93, 95%CI 0.83 to 1.14, P=0.73）. And the results of TSA displayed that all of the cumulative Z-curve did not strode both TSA threshold value and required information size line excepting for DD vs. DI＋II genetic model which suggested

关 键 词：肽基二肽酶A 多态现象 遗传 骨性关节炎 META分析 试验序贯分析 

分 类 号：R684.3[医药卫生—骨科学]