CTLA4基因多态性与炎症性肠病遗传易感性相关性研究

Correlative Analysis between CTLA-4 Gene Polymorphism and Sus-ceptibility of Inflammatory Bowel Disease

目的：系统评价细胞毒性T淋巴细胞相关抗原4（ CTLA-4）基因多态性与炎症性肠病发病风险的相关性。方法计算机检索PubMed、 EMbase、 WanFang Data、 CNKI、 CBM和VIP，查找关于CTLA4基因多态性与炎症性肠病发病风险的病例-对照研究，检索时限均从建库至今。2名评价员按照纳入与排除标准独立筛选文献、提取资料并评价纳入研究的方法学质量后，采用RevMan5．2和Stata12．0软件进行Meta分析。结果纳入2个CTLA？4基因位点： rs231775，及非转录区（ AT） n重复序列微卫星片段，共10个研究。 Meta分析结果显示： CTLA-4-rs231775基因非转录区（ AT） n重复序列多态性与炎症性肠病发病风险有相关性： rs231775多态性增加人群克罗恩病易感性[AG＋GG vs． AA： OR＝1．29，95％CI （1．05～1．59）， P＝0．02。 GG vs． AA： OR＝2．14，95％CI （1．14～4．04）， P＝0．02]； CTLA？4基因非转录区（AT）n重复序列≥118 bp片段人群组发生溃疡性结肠炎的可能性是非≥118 bp片段组的4．85倍（ P＜0．05），前者发生克罗恩病的可能性是后者的3．82倍（P＜0．05）， CTLA？4基因非转录区（AT）n重复序列122 bp片段人群发生溃疡性结肠炎的可能性是非122 bp片段的15．5倍（ P＜0．05）。结论 CTLA？4？rs231775基因非转录区（ AT） n重复序列多态性会增加炎症性肠病发病风险。但鉴于纳入研究数量有限，尚需开展更多研究予以验证。

Objective To systematically evaluate the association of cytotoxic T lymphocyte-as-sociated antigen-4 （ CTLA-4 ） polymorphism with the risk of inflammatory bowel disease （ IBD ） . Methods All eligible case-control studies published up to now were identified by searching PubMed, EMbase, WanFang Data, CNKI, CBM and VIP. Two reviewers independently screened the studies according to the inclusion and exclusion criteria, extracted data and assessed methodo-logical quality of included studies. Then, the meta-analysis was performed using RevMan 5. 2 and Stata 12. 0 software. Results A total of 10 studies involving the association between CTLA-4-rs231775 or the （ AT） n repeat in the untranslated region and the susceptibility to IBD were includ-ed. This meta-analysis showed that a strong association between CTLA-4 gene polymorphism and the risk of IBD. CTLA-4-rs231775 increased the risk of Crohn’ s disease （ CD） [ AG＋GG vs. AA： OR=1. 29 , 95% CI （ 1. 05 – 1. 59 ） , P =0. 02; GG vs. AA： OR =2. 14 , 95% CI （ 1. 14 –4. 04 ） , P=0. 02 ] . The risk of ulcerative colitis （ UC ） was increased 4. 85 times in people with the allele （≥118 bp） of （AT）n repeat fragments as compared with those without （P〈0. 05） . The risk of CD in the former was increased 3. 82 times as compared with the latter （ P〈0. 05 ） , and the＆amp;nbsp;risk of UC was elevated even 15. 5 times in people with the allele （122 bp） of （ AT） n repeat frag-ments as compared with those without （ P〈0. 05 ） . Conclusion CTLA-4-rs231775 and the allele of （ AT） n repeat fragments may increase the risk of IBD.