Department of Dermatology, Hospital Kuala Lumpur, Ministry of Health Malaysia.
Department of Dermatology, Hospital Serdang, Ministry of Health Malaysia.
Pharmacogenet Genomics. 2020 Sep;30(7):153-160. doi: 10.1097/FPC.0000000000000408.
The association between human leukocyte antigen (HLA)-B58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined.
We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC).
HLA-B58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B58:01 positive). HLA-B58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive.
Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN.
在不同人群中观察到人类白细胞抗原（HLA）-B58:01 与别嘌醇诱导的严重皮肤不良反应（AIS）风险之间存在关联。我们探索 HLA-B58:01 与马来西亚多民族人群 AIS 风险之间的关联。确定了 HLA-B*58:01 与不同 AIS 临床表型和种族的相关性。
我们通过对 55 例 AIS 患者（11 例中毒性表皮坏死松解症（TEN）、21 例史蒂文斯-约翰逊综合征（SJS）、22 例药物反应伴嗜酸性粒细胞增多和全身症状（DRESS）和 1 例急性全身性发疹性脓疱病（AGEP））和 42 例别嘌醇耐受对照者（ATC）的 HLA-B 等位基因进行基因分型，进行病例对照关联研究。
AIS 和 ATC 研究组中 HLA-B58:01 阳性率分别为 89.1%和 14.3%（优势比（OR）=49.0，95%置信区间（CI）=14.6-164.4，P<0.0001））。我们的数据显示，93.8%的 AIS-SJS/TEN 患者和 86.4%的 AIS-DRESS 患者为 HLA-B58:01 阳性（AIS-SJS/TEN，OR=90，95%CI=16.9-470.1，P<0.0001 和 AIS-DRESS OR=38，95%CI=8.5-169.2，P<0.0001））。按种族和临床表型分层显示，HLA-B58:01 与中国 AIS 患者之间存在显著的风险增加（OR=137.5，95%CI=11.3-1680.2，P<0.0001），特别是中国 AIS-SJS/TEN 患者（100%HLA-B58:01 阳性）。90.9%的中国 AIS-DRESS 患者 HLA-B58:01 阳性（P<0.0001）。在马来裔 AIS-SJS/TEN（OR=78，95%CI=9.8-619.9，P<0.0001）和马来裔 AIS-DRESS（OR=54，95%CI=6.6-442.9，P<0.0001）中也观察到 HLA-B58:01 的高度显著相关性。虽然印度裔 AIS 患者的数量相对较少（n=2），但两者均为 HLA-B*58:01 阳性。
我们的数据表明，HLA-B*58:01 与马来西亚人群中的 AIS 之间存在强烈关联，其中包括华裔和马来裔。在 AIS 的三种不同临床表型中也观察到了强烈的相关性，主要是 AIS-SJS/TEN。
