白细胞介素10基因启动子多态性与多发性硬化发病关系的meta分析

Association between interleukin-10 gene promoter polymorphisms and multiple sclerosis:a meta-analysis

目的探讨白细胞介素10基因启动子多态性-1082G/A、-819C/T和-592C/A与多发性硬化（multiple sclerosis,MS）发病的关系。方法在PubMed、EBSCO、Ovid、EMbase、CNKI、万方科技与维普数据库中系统性检索1990年1月1日至2015年1月31日发表的相关文献,在等位基因、显性遗传、隐性遗传和共显性遗传4类模型下,合并OR值和95%CI,并行敏感性分析和发表偏倚评估。结果共纳入10篇文献,病例组1 483例,对照组1 796例。在所有模型中,-1082、-819位点基因分布在MS组与对照组间差异无统计学意义。但隐性遗传模型（AA vs GA＋GG）显示复发缓解型＋继发进展型MS亚组与对照组在-1082位点上的基因分布差异有统计学意义（OR=0.729,95%CI=0.534-0.995,P〈0.05）。等位基因模型（A vs C）（OR=0.825,95%CI=0.683-0.998,P〈0.05）、显性遗传模型（AA＋CA vs CC）（OR=0.764,95%CI=0.605-0.966,P〈0.05）和杂合子模型（CA vs CC）（OR=0.750,95%CI=0.585-0.960,P〈0.05）表明MS组与对照组在-592位点上的基因分布差异有统计学意义。敏感性分析显示,除-819位点杂合子模型和-592位点等位基因模型结果不稳健外,3个位点各模型均稳健。未发现明显发表偏倚。结论 -1082位点AA基因型对复发缓解型及继发进展型MS的发生具有保护作用;-592位点CA基因型对MS的发生具有保护作用,而CC基因型携带者更易发生MS;-819位点CT基因型相对于CC基因型携带者可能不易发生MS。

Objective To explore the assosiction between interleukin-10（IL-10）gene promoter polymorphisms（-1082G/A,-592C/A and-892C/T）and multiple sclerosis（MS）.Methods The data were collected from the Pubmed,EBSCO,Ovid,EMbase,CNKI library,WANFAN data and VIP,and the references of eligible studies were manually screened from Jan 1,1990 to Jan 31,2015.A standard meta-analysis approach was conducted on the associations between IL-10 promoter polymorphisms（-1082G/A,-592C/A and-892C/T）and MS using allele contrast,recessive,dominant,and co-dominant models.The combined odds ratio（OR）with 95%confidence interval（CI）was calculated to test heterogeneity and sensitivity analysis.Results A total of 10 studies involving 1 483 cases and 1 796 controls were considered in this meta-analysis.All the four models showed that neither the presence of genotypes nor the frequency of alleles differed significantly between MS patients and controls at-1082and-819 site.However,in subgroup analysis,the AA versus GA＋GG genotype was significantly different between relapsingremitting（RR）/secondary-progressive（SP）MS patients and controls at-1082site（OR =0.729,95%CI =0.534-0.995,P 〈0.05）.At-592 site,there were significant differences in the allele contrast（A vs C）（OR =0.825,95%CI =0.683-0.998,P 〈0.05）,dominant（AA＋CA vs CC）（OR =0.764,95%CI =0.605-0.966,P 〈0.05）and codominant（CA vs CC）（OR =0.750,95%CI =0.585-0.960,P 〈0.05）models.The sensitivity analysis showed the results were all stable except the presence of CT versus CC at-819 site and A versus C at-592 site.Conclusion The AA genotype at-1082 site was associated with the low risk of RRMS and SPMS.At-592 site,CA genotype was associated with the low risk of MS,while the patients with CC genotype were more likely to suffer from MS.The patients with CT genotype at-819 site might reduce the susceptibility of MS rather than CC genotype.