HLA-DQA1 and DQB1 Alleles are Associated with Acitretin Response in Patients with Psoriasis
HLA-DQA1 and DQB1 Alleles are Associated with Acitretin Response in Patients with Psoriasis
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HLA-DQA1 和 DQB1 等位基因与银屑病患者的阿维A反应相关
DOI：
10.31083/j.fbl2709266
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Wu Zhu
中科院分区：
文献类型：
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作者：
Xingchen Zhou;Yijing He;Yehong Kuang;Wangqing Chen;Wu Zhu
背景：寻常型银屑病是一种免疫介导的炎症性皮肤病。虽然银屑病的发病机制尚不清楚，但遗传易感性，如人类白细胞抗原-C*06：02，被认为是一个主要的危险因素。然而，关于遗传学与银屑病系统治疗反应之间的关系的知识很少。我们假设人类白细胞抗原(HL A)基因的遗传变异可以作为阿维A治疗银屑病的预测因子。我们研究的目的是探讨接受阿维A治疗的中到重度银屑病患者中是否存在人类白细胞抗原基因变异。方法：共100例汉族人银屑病患者完成研究。24例患者，包括16例应答者和8例无应答者，采用MHC靶区捕捉法进行深度测序，并对76例样本进行基于Sanger测序(SBT)的基因分型验证。结果：经年龄、性别、体重指数(BMI)、银屑病面积和严重程度指数(PASI)调整后的回归分析显示，两个HLA等位基因(HLADQA1*：02：01，DQB*：02：02)与阿维A的疗效相关。DQA10201阳性患者对阿维A的疗效好于DQA10201阴性患者(相对危险度RR=10.34，95%可信区间2.62~40.77，P=0.001)；DQB10202阳性患者对阿维A的疗效好于DQB10202阴性患者(RR=21.01，95%CI：2.53~174.27，P=0.005)。结论：我们的观察结果支持人类白细胞抗原-DQA1*：02：01和DQB*：02：02作为银屑病患者阿维A反应的潜在药物遗传学标志物。
Background: Psoriasis vulgaris is an immune-mediated inflammatory skin disease. Although the pathogenesis of psoriasis is unclear, genetic susceptibility, such as HLA-C*06:02, is believed to be a major risk factor. However, there is a paucity of knowledge regarding the relationship between genetics and the response to systemic treatment of psoriasis. We hypothesized that genetic variations in human leukocyte antigen (HLA) genes may act as predictors of acitretin treatment in psoriasis. The aim of our study was to explore the presence of HLA gene variants in patients with moderate-to-severe psoriasis receiving acitretin treatment. Methods: A total of 100 Han Chinese patients with psoriasis completed the study. 24 patients including 16 responders and 8 non-responders underwent deep sequencing by MHC targeted region capture and 76 samples were genotyped by Sanger sequencing (SBT) based HLA typing for validation. Results: Regressions with adjustment for age, sex, body mass index (BMI), and baseline psoriasis area and severity index (PASI) revealed that two HLA alleles (HLA-DQA1*:02:01, DQB*:02:02) were associated with the response to acitretin. The DQA1*0201-positive patients showed a better response to acitretin compared to the DQA1*0201-negative patients (relative risk (RR) = 10.34, 95% confidence interval (CI): 2.62–40.77, p = 0.001), and the DQB1*0202-positive patients manifested a better response to acitretin when compared to the DQB1*0202-negative patients (RR = 21.01, 95% CI: 2.53–174.27, p = 0.005). Conclusions: Our observations support the potential role of HLA-DQA1*:02:01 and DQB*:02:02 as pharmacogenetic markers of the acitretin response in patients with psoriasis.