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HLA-DR等位基因对类风湿关节炎的影响:阿根廷患者的易感性和严重程度

Influence of HLA-DR alleles on rheumatoid arthritis: susceptibility and severity in Argentine patients.

作者信息

Citera G, Padulo L A, Fernandez G, Lazaro M A, Rosemffet M G, Maldonado Cocco J A

机构信息

Department of Rheumatology, Hospital de Clínicas José de San Martín, School of Medicine, University of Buenos Aires, Argentina.

出版信息

J Rheumatol. 2001 Jul;28(7):1486-91.

PMID:11469451
Abstract

OBJECTIVE

To determine the frequency of shared epitopes in our population of patients with rheumatoid arthritis (RA) and to investigate whether the presence of these alleles is associated with a more aggressive form of disease.

METHODS

Demographic and clinical data were obtained from 140 patients with RA, 123 female, mean age 49.9+/-11.7 years and mean disease duration 9.4+/-6.3 years. Radiographs of both hands were taken and scored by Larsen's method. HLA-DR alleles were determined by PCR-SSP. The control group comprised 202 healthy ethnic-matched subjects.

RESULTS

DR4 was significantly more frequent in patients with RA than controls, and was observed in 70/140 patients (50%) versus 47/202 controls (23.27%) (odds ratio 3.25, CI 1.99-5.35, Pcorr 5 x 10(-5)). Within DR4 subtypes *0404 and *0401 were the most commonly found (37.7 and 29%, respectively). DR3 and DR11 exerted a protective effect with significantly higher frequency in controls than in patients with RA. When patients were divided into 2 groups according to disease severity (radiographic score) the frequency of alleles with QKRAA and QRRAA sequences was similar in both groups. Although with lower frequency, subtype *1001 alone was significantly more frequent in the severe-condition group [7 (13.5%) vs 3 (3.4%), p = 0.03].

CONCLUSION

These results are in accordance with findings observed in Caucasians and differ from other Latin American populations. However shared epitope alleles failed to correlate with more severe disease with the exception of subtype *1001 which, although infrequent, was significantly more frequent in patients with relevant radiological damage.

摘要

目的

确定类风湿关节炎(RA)患者群体中共享表位的频率,并研究这些等位基因的存在是否与更具侵袭性的疾病形式相关。

方法

从140例RA患者中获取人口统计学和临床数据,其中123例女性,平均年龄49.9±11.7岁,平均病程9.4±6.3年。拍摄双手X光片并采用Larsen方法评分。通过聚合酶链反应-序列特异性引物(PCR-SSP)确定HLA-DR等位基因。对照组包括202名种族匹配的健康受试者。

结果

RA患者中DR4的频率显著高于对照组,70/140例患者(50%)出现DR4,而202例对照组中为47/202例(23.27%)(优势比3.25,可信区间1.99 - 5.35,校正P值5×10⁻⁵)。在DR4亚型中,0404和0401最常见(分别为37.7%和29%)。DR3和DR11具有保护作用,在对照组中的频率显著高于RA患者。根据疾病严重程度(X光评分)将患者分为两组时,具有QKRAA和QRRAA序列的等位基因频率在两组中相似。尽管频率较低,但仅*1001亚型在重症组中显著更常见[7(13.5%)对3(3.4%),p = 0.03]。

结论

这些结果与在白种人中观察到的结果一致,与其他拉丁美洲人群不同。然而,除了*1001亚型外,共享表位等位基因与更严重的疾病无关,*1001亚型虽然不常见,但在有相关放射学损伤的患者中显著更常见。

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