简报：HLA-DRB1 易感等位基因对韩国系统性红斑狼疮临床亚型的影响。

Brief Report: Influence of HLA-DRB1 Susceptibility Alleles on the Clinical Subphenotypes of Systemic Lupus Erythematosus in Koreans.

机构信息

Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.

Kyung Hee University Hospital, Seoul, Republic of Korea.

出版信息

Arthritis Rheumatol. 2016 May;68(5):1190-6. doi: 10.1002/art.39539.

DOI:10.1002/art.39539

PMID:26663868

Abstract

OBJECTIVE

To investigate the association between HLA-DRB1 alleles and systemic lupus erythematosus (SLE) susceptibility and features of SLE, such as clinical manifestations and autoantibody profiles, in a Korean population.

METHODS

We tested the genetic associations between HLA-DRB1 alleles and SLE susceptibility and clinical subphenotypes in 1,089 patients with SLE and 2,161 control subjects, including a discovery set (475 patients and 1,119 controls) and a replication set (614 patients and 1,042 controls). We used a relative predispositional effects (RPEs) method to examine the independent effect of each allele associated with SLE or its subphenotypes.

RESULTS

We identified 4 HLA-DRB1 alleles that were associated with increased susceptibility to SLE, 2 of which had been detected previously (*15:01; P for RPE = 1.11 × 10(-13) , odds ratio [OR] 1.88) and *09:01 (P for RPE = 1.59 × 10(-5) , OR 1.46), and 2 of which were novel alleles (*08:03 [P for RPE = 8.80 × 10(-8) , OR 1.62]) and 07:01 (P for RPE = 1.14 × 10(-6) , OR 1.57)]. In addition, protective effects on the development of SLE were observed for 2 novel alleles (HLA-DRB112:02 [P for RPE = 6.35 × 10(-4) , OR 0.49]) and 11:01 [P for RPE = 1.24 × 10(-3) , OR 0.59]). The SLE risk alleles had an additive genetic effect, as demonstrated by the finding that double copies of these alleles (OR 3.38) had larger risk effects size compared with single copies (OR 1.95) and no copy (OR 1 [reference]). In a subphenotype analysis, various HLA-DRB1 alleles (including SLE risk alleles) were observed to have significant predispositional effects on diverse clinical manifestations. In particular, HLA-DRB115:01 (OR 2.30), *09:01 (OR 2.46), *07:01 (OR 2.61), and *08:03 (OR 2.97) were strongly associated with the risk of anti-Sm antibody production.

CONCLUSION

We detected 6 HLA-DRB1 alleles that were associated with SLE in Koreans. The SLE risk alleles promoted the production of autoantibodies, including anti-Sm, and diverse clinical manifestations.

摘要

目的

在韩国人群中，研究 HLA-DRB1 等位基因与系统性红斑狼疮（SLE）易感性以及 SLE 的特征（如临床表现和自身抗体谱）之间的关联。

方法

我们在 1089 例 SLE 患者和 2161 例对照中检测了 HLA-DRB1 等位基因与 SLE 易感性和临床亚表型之间的遗传关联，包括发现集（475 例患者和 1119 例对照）和验证集（614 例患者和 1042 例对照）。我们使用相对易感性效应（RPE）方法来检测与 SLE 或其亚表型相关的每个等位基因的独立效应。

结果

我们鉴定出了 4 个与 SLE 易感性增加相关的 HLA-DRB1 等位基因，其中 2 个先前已被发现（15:01；RPE 的 P 值为 1.11×10(-13)，OR 1.88）和09:01（P for RPE = 1.59×10(-5)，OR 1.46），另外 2 个是新的等位基因（08:03 [P for RPE = 8.80×10(-8)，OR 1.62]和07:01 [P for RPE = 1.14×10(-6)，OR 1.57]）。此外，我们还观察到了 2 个新的等位基因（HLA-DRB112:02 [P for RPE = 6.35×10(-4)，OR 0.49]和11:01 [P for RPE = 1.24×10(-3)，OR 0.59]）对 SLE 的发生具有保护作用。SLE 风险等位基因具有累加遗传效应，这一点可以从这些等位基因的双拷贝（OR 3.38）比单拷贝（OR 1.95）和无拷贝（OR 1[参考]）具有更大的风险效应大小中得到证明。在亚表型分析中，各种 HLA-DRB1 等位基因（包括 SLE 风险等位基因）均被观察到对多种临床表现具有显著的倾向性效应。特别是，HLA-DRB1*15:01（OR 2.30）、*09:01（OR 2.46）、07:01（OR 2.61）和08:03（OR 2.97）与抗 Sm 抗体产生的风险密切相关。