IL-10基因启动子区域-592(A/C)和-1082(A/G)位点多态性与系统性红斑狼疮相关性的Meta分析

Meta-analysis on the correlation between the polymorphism of IL-10 gene promoter region -592(A/C) and -1082(A/G) and systemic lupus erythematosus

目的评价白介素-10（IL-10）基因启动子区域592（A／C）及-1082（A／G）位点多态性与系统性红斑狼疮（SLE）的关系。方法通过电子检索PubMed、EMBASE、Cochrane Central Register of Controlled Trials、中国知网（CNKI）、中国生物医学文献数据库（CBMD）、维普等常用的中外文数据库，采用主题词结合自由词的检索方法，检索时间从建库至2013-04—15。对检索到的文献进行筛选后，利用Meta分析（荟萃分析）对IL-10基因启动子区域592（A／C）、-1082（A／G）位点基因多态性与SLE发病风险之间的关联进行分析，使用基因频率对比、显性及隐性等遗传模式，对比两位点基因型或等位基因频率分布在病例组与对照组间的差异。用Stata 11．0软件进行Meta分析。结果本研究共纳入该两位点合格文献10篇，其中6篇文献同时涉及两个位点。在文献研究和资料检索中未发现两个位点有连锁不平衡现象，按照独立的基因多态性位点进行分析。其中-592（A／C）位点纳入文献8篇，Meta分析的结果显示，在总人群中，3种模型下差异均无统计学意义；对人群按照人种进行亚组分析后发现，欧洲人群A／C等位基因频率分布（OR=1．21，95％CI=1．011～1．456，P=0．040）及显性模型下（OR=2．53，95％CI=1．642～3．904，P〈0．01）分布的差异有统计学意义；而亚裔人群中3种模型差异均有统计学意义（Aus C：OR=0．84，95％CI=0．739～0．962，P〈0．01；隐性：OR=0．56，95％CI=0．472～0．662，P〈0．01；显性：OR=0．65，95％CI=0．481～0．870，P〈O．01），且在欧裔中A等位基因相对C为危险因素，在亚洲人群中则是保护因素。另外，-1082（A／G）位点纳入文献8篇，Meta分析的结果显示，总人群的3个模型下差异均无统计学意义且有较大的异质性；因此按人群亚组分析后，欧裔人群中A／C等位基因在两组中的分布差异有统计学意义（OR=1．30，95％CI=1．101～1．547，P〈0．01）；亚裔人群中显性模型（OR=0.35，95％CI=0．199-0．607，P〈0．01）下差异有统计学意义。结论IL-10启动子区域的-592（A／C）、-1082（A／G）位点多态性可能与SLE的易感性相关，但是有种族人群的差异。

Objective To assess the correlation between the polymorphism of interleukin-10 （IL-10） gene promoter region-592 （A/C） and-1082 （A/G） and systemic lupus erythematosus （SLE）. Methods Study related publications searched in commonly used database such as CNKI, VIP database, Cochrane Central Register of Controlled Trials databases, Pubmed and EMBASE were retrieved and analyzed using Meta-analysis method. The allele frequency contrast, dominance and recessive genetic model were used to compare the differences of genotypes and allele frequency distribution between the case group and control group. Results A total of 10 papers were selected, and 6 of them had both sites polymorphisms. The analysis was based on single site polymorphism because there was no consecutive imbalance between these two sites. Meta- analysis found no significantly positive correlation between 592 （A/C） polymorphism and SLE under all genetic models in gross populations after 8 related articles were analyzed in which 1 715 cases and 1 974 controls included. However, positive correlations were found in European subgroup under both A/C allele frequency contrast （OR=1.21, 95;CI： 1.011 1.456, P=0.040） and dominance genetic model （OR=2.53, 95; CI： 1. 642-3. 904, P〈0.01）, as well as in Asian subgroup under all three genetic models （A/C： OR= 0.84, 95;CI： 0.739-0.962, P〈0.01; recessive： 0R=0.56, 95;CI： 0.472-0.662, P〈0.01; dominance： OR=0. 65, 95;CI： 0. 481-0. 870, P〈0.01）. The result also showed that A allele was a risk factor in European subgroup while in Asian it was a protective one. In terms of the correlation between -1082 （A/G） and SEL, 8 related articles including 1 321 cases and 1 939 controls were also analyzed and showed a significant heterogeneity and no significant association found under all genetic models in gross population. But in European subgroup, A allele was found to be a risk factor compared to G allele （OR=1. 30, 95%CI： 1. 101- 1. 547, P〈0.01）and in Asian subgroup the correlation was positive only under dominance genetic model （OR =0.35, 95%CI： 0. 199 0. 607, P〈0.01）. Conclusions The polymorphisms of IL-10 promoter region - 592 （A/C） and -1082 （A/G） may be related to the SLE susceptibility. But it varies among different ethnic groups.