强直性脊柱炎遗传易感性和白细胞介素-1基因多态性的荟萃分析

目的评价白细胞介素（IL）-1基因多态性与强直性脊柱炎（AS）发病的相关性。方法利用荟萃分析的方法综合已发表的相关文献中的研究数据。检索Pubmed、EMBASE、Coehrane图书馆和中国生物医学文献数据库（CBM）,收集所有AS相关的病例对照研究。纳入标准：纳入文献内容涉及白细胞介素（IL）-1基因多态性与AS的病例对照研究;AS诊断按照1984年修订的纽约诊断标准,由风湿专科医生作出诊断;原始数据提供等位基因频率和／或基因型频率;被研究位点在对照人群中符合Hardy-Weinberg平衡。剔除标准：不符合纳入标准,重复报道及家系研究。结果（1）经全面检索纳入6篇文献,共9个研究人群。总体数据合并统计呈明显异质性。分别按高加索人种和蒙古人种进行分层后亚组内各研究间具有同质性。（2）荟萃分析显示,IL-1RN第2内含子中的数目可变串联重复（VNTR）多态性等位基因2在高加索人种AS患者中频率增高,该等位基因OR=1．52（95％CI=1．26～1．84,P〈0．01）,相应基因型OR=1．33（95％CI=1．04～1．70,P〈0．05）;但是,该等位基因在蒙古人种AS患者中的频率比对照组低,等位基因OR=0．55（95％CI=0．38～0．81,P〈0．01）,基因型OR=O．51（95％CI=O．34～0．77,P〈0．01）。（3）IL-1A-889C〉T（rs1800587）的次要等位基因T在高加索人种AS患者中频率增高,OR=1．36（95％CI=1．12～1．66,P〈0．01）,相应基因型C／T＋T／T的OR=1．56（95％CI=1．20～2．03,P〈0．01）。但在蒙古人种人群中差异无统计学意义。（4）在高加索人种人群中,IL-1F8的SNP rs1900287的次要等位基因G在AS患者中频率增加,OR=1．22（95％CI=1．04～1．44,P〈0．05）。结论作为一种复杂性状疾病,AS发病的遗传易感因素可能与IL-1基因多态性相关,相关的多态性位点有IL-1RN第2内含子86bpVNTR、IL-1A-889 C〉T（rs1800587）和IL-1F8的SNP rs1900287。IL-1基因多态性与疾病的关联有明显的人种差异。

A meta-analysis on interleukin-1 gene cluster polymorphism and genetic susceptibility for ankylosing spondylitis

OBJECTIVE: To investigate the association between interleukin (IL)-1 gene cluster polymorphism and the genetic susceptibility for ankylosing spondylitis (AS). METHODS: Relevant published data were retrieved through Pubmed, EMBASE, Cochrance library and Chinese Bio-medicine Database (CBM). Studies eligible for this meta-analysis had to meet all the following inclusion criteria: (1) the content was associated with population-based case-control studies, (2) the study was on the relationship between the IL-1 gene cluster polymorphism and AS, (3) the diagnosis of AS was based on the modified New York criteria (1984) by the rheumatologist. (4) the raw data including the frequencies of alleles and certain genotypes in case and control groups could be collected. and (5) the distribution of studied loci in the populations was in accord with the Hardy-Meinberg equilibrium. Researches that didn't meet the inclusion criteria, as well as the duplicated reports, family-based studies were excluded. All analyses were conducted with the software 'Review Manager' Version 4.2.8. RESULTS: (1) A total of 6 literatures, including 9 population samples, were studied. The overall combined data were verified to be heterogeneous, and the heterogeneity disappeared after stratification by the race. Then, the fixed-effect model could be applied. (2) The combined data revealed the frequencies of allele 2 and its genotypes of IL-1RN intron 2 variable number of tendem repeats were higher in the AS groups than in the controls in the Caucasian population (allele 2: OR=1.52, 95% CI=1.26 approximately 1.84, P<0.01; genotype: OR=1.33, 95% CI=1.04 approximately 1.70, P<0.05), but lower in the AS groups than in the controls in the Mongolian population (allele 2: OR=0.55, 95% CI=0.38 approximately 0.81, P<0.01; genotype: OR=0.51, 95% CI=0.34 approximately 0.77, P<0.01). (3) The minor allele T of IL-1A -889C>T (rs1800587) was higher in the AS group than in the controls in the Caucasian population (allele T: OR=1.36, 95% CI=1.12 approximately 1.66, P<0.01; genotype C/T+T/T: OR=1.56, 95% CI=1.20 approximately 2.03, P<0.01). This distribution could not be found in the Mongolian population for this SNP. (4) The minor allele G of IL-1F8 SNP (rs1900287) was higher in the AS group than in the controls in the Caucasian population (OR=1.22, 95% CI=1.04 approximately 1.44, P<0.05). CONCLUSION: The genetic susceptibility for AS may be associated with the IL-1 gene cluster polymorphism. The relevant polymorphic sites include IL-1RN 86bp VNTR in intron 2, IL-1A -889C>T (rs1800587) and IL-1F8 SNP (rs1900287). Furthermore, there is a distinct discrepancy for this association among races.