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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、Cochrane 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=0.51(95%CI=0.34～0.77,P<0.01)。(3)IL-1A-889 C>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86 bpVNTR、IL-1A-889C>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。
Objective To evaluate the association between interleukin (IL) -1 gene polymorphism and the pathogenesis of ankylosing spondylitis (AS). Methods A meta-analysis approach was used to synthesize published research data from relevant literature. Pubmed, EMBASE, the Cochrane Library and China Biomedical Literature Database (CBM) were searched and all AS-related case-control studies were collected. Inclusion criteria: A case-control study of the polymorphism of the interleukin (IL) -1 gene with AS was included in the literature; AS diagnosis was diagnosed by a rheumatologist based on New York diagnostic criteria as revised in 1984; raw data provided alleles Frequency and / or genotype frequency; the site studied matches the Hardy-Weinberg equilibrium in the control population. Exclusion Criteria: Does not meet the inclusion criteria, repeated coverage and pedigree studies. Results (1) A total of 6 articles were included in the study after comprehensive search. Overall data consolidation statistics showed significant heterogeneity. There was homogeneity among the studies in the subgroup after being stratified by Caucasian race and Mongoloid race, respectively. (2) Meta-analysis showed that the frequency of variable tandem repeat (VNTR) polymorphism allele 2 in IL-1RN intron 2 was increased in Caucasian AS patients with OR = 1.52 ( 95% CI = 1.26-1.84, P <0.01). The corresponding genotype OR was 1.33 (95% CI = 1.04-1.70, P <0.05). However, the frequency of this allele in Mongolian patients with AS was higher than that in controls The odds ratio was 0.55 (95% CI = 0.38-0.81, P <0.01). The genotype OR was 0.51 (95% CI = 0.34-0.77, P <0.01). (3) The frequency of secondary allele T in IL-1A-889 C> T (rs1800587) was significantly higher in Caucasian AS patients (OR = 1.36, 95% CI = 1.12-1.66, P <0.01) Type C / T + T / T OR = 1.56 (95% CI = 1.20-2.03, P <0.01). However, there was no significant difference in Mongolian population. (4) In Caucasian population, the frequency of G allele G of SNP rs1900287 in IL-1F8 increased in patients with AS, OR = 1.22 (95% CI = 1.04-1.44, P <0.05). Conclusions As a complex trait disease, the genetic predisposing factors of AS may be related to the polymorphism of IL-1 gene. The related polymorphic sites include IL-1RN second intron 86 bpVNTR, IL-1A-889C > T (rs1800587) and SNP rs1900287 for IL-1F8. The association of IL-1 gene polymorphism with disease has significant ethnic differences.