Impact of shared epitope genotype and ethnicity on erosive disease - A meta-analysis of 3,240 rheumatoid arthritis patients
Impact of shared epitope genotype and ethnicity on erosive disease - A meta-analysis of 3,240 rheumatoid arthritis patients
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DOI：
10.1002/art.20006
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发表时间：
2004-02-01
影响因子：
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通讯作者：
Criswell, LA
中科院分区：
文献类型：
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作者：
Gorman, JD;Lum, RF;Criswell, LA
Objective.类风湿性关节炎（RA）中已知最强的遗传关联是与HLA-DRB 1等位基因共享相似的氨基酸序列，称为共享表位（SE）。虽然许多研究已经检查了SE与疾病严重程度的关联，但结果不一致，这可能反映了样本量相对较小或种族差异。本研究的目的是通过荟萃分析评估HLA-DRB 1 SE等位基因和基因型与RA骨侵蚀发展的相关性。我们通过Medline、EMBase和人工检索6种相关期刊，确定了1987年1月1日至1999年6月1日期间发表的英文文章。包括进行HLA-DRB 1等位基因分子分型和报告骨侵蚀存在或不存在的研究。从研究中提取数据，并将糜烂编码为存在或不存在。联系作者以获取缺失的信息和个体患者的数据。共有29项研究和3，240例患者可用于分析。当所有患者作为一个单一组进行评估时，总结比值比（OR）显示SE（2或1对0 SE等位基因）的存在与糜烂显著相关（OR 2.0; 95%置信区间[95% CI] 1.8-2.2），尽管存在显著异质性（P = 0.002）。亚组分析表明，种族背景的重要影响。例如，在希腊人中没有证实SE与糜烂相关（OR 0.8 [95% CI 0.2-1.5]）。相比之下，在南欧高加索人和亚洲人中存在显著的剂量依赖性关系，在具有2个SE等位基因的患者中，OR分别高达6.2和5.4。尽管我们评估SE基因型与糜烂关系的能力有限，但在一项仅限于北方欧洲高加索人的分析中，DRB 1 *0401 SE等位基因特别重要。在许多种族中，SE与糜烂性疾病的发展有关;然而，存在明显的例外。这些变异可能是由于人群之间的等位基因差异，例如DRB 1 *0401在不同种族群体中的频率。进一步的研究，以更好地了解这些人群之间的遗传和环境差异，可能会提供深入了解影响RA临床表现的机制。
Objective. The strongest known genetic association in rheumatoid arthritis (RA) is with HLA-DRB1 alleles that share a similar amino acid sequence, termed the shared epitope (SE). Although many studies have examined the association of the SE with disease severity, the results have been inconsistent, which may reflect the relatively small sample sizes or ethnic differences. The aim of this study was to assess the association of HLA-DRB1 SE alleles and genotype with the development of bony erosions in RA by meta-analysis.Methods. We identified English-language articles published between January 1, 1987 and June 1, 1999 through Medline, EMBase, and manual searches of 6 relevant journals. Included were studies in which molecular typing of HLA-DRB1 alleles was performed and in which the presence or absence of bony erosions was reported. Data were extracted from the studies, and erosions were coded as present or absent. Authors were contacted for missing information and data on individual patients.Results. A total of 29 studies and 3,240 patients were available for analysis. The summary odds ratios (ORs), when all patients were evaluated as a single group, demonstrated a significant association of the presence of the SE (2 or 1 versus 0 SE alleles) with erosions (OR 2.0; 95% confidence interval [95% CI] 1.8-2.2), although significant heterogeneity was present (P = 0.002). Subgroup analyses demonstrated the important influence of ethnic background. For example, no association of the SE with erosions was demonstrated in Greeks (OR 0.8 [95% CI 0.2-1.5]). In contrast, there was a striking dose-dependent relationship in southern European Caucasians and Asians, with ORs as high as 6.2 and 5.4, respectively, in patients with 2 SE alleles. Although our ability to assess the relationship between SE genotype and erosions was limited, particular importance of the DRB1*0401 SE allele was suggested in an analysis restricted to northern European Caucasians.Conclusion. The SE is associated with the development of erosive disease in many ethnic groups; however, striking exceptions exist. These variations may be due to allele differences between populations, such as the frequency of DRB1*0401 among different ethnic groups. Further study to better understand the genetic and environmental differences between these populations may provide insight into mechanisms that influence the clinical expression of RA.