未经证实:HLA-B*58:01是众所周知的别嘌呤醇引起的严重皮肤不良反应(SCAR)的危险因素。然而,只有少数HLA-B*58:01携带者在服用别嘌呤醇后出现SCAR。这项研究的目的是研究辅助遗传标记,这些标记可以鉴定在HLA-B*58:01受试者中进一步增加的具有嗜酸性粒细胞增多和全身症状(DRESS)的别嘌呤醇诱导的药物反应的风险。
UNASSIGNED:纳入了B*58:01受试者(21名别嘌醇诱导的DRESS和52名别嘌醇耐受对照)。HLA-A,-B,比较-C和-DRB1等位基因。在不同人群中进行HLA和别嘌呤醇诱导的SCAR之间的风险比较以支持结果。Kruskal-Wallis测试,皮尔森卡方检验,采用Fisher精确检验和二元logistic回归分析SCAR发生的风险。
未经评估:A*24:02的频率(71.4vs.17.3%,p<0.001,比值比[OR]=12.0;95%置信区间[CI],3.6-39.2)在B*58:01()DRESS中明显高于B*58:01()耐受性对照。此外,DRB1*13:02进一步增加了DRESS的风险。B*58:01(+)DRESS组的A*24:02/DRB1*13:02表型频率显著高于B*58:01(+)耐受对照(52.4%vs.5.8%,p<0.001,或,66.0;95%CI,6.1-716.2)。在2782个别嘌醇用户队列中,DRESS的总体患病率为0.22%,在存在B*58:01和B*58:01/A*24:02的情况下,分别增加到1.62%和2.86%。
UNASSIGNED:使用A*24:02和DRB1*13:02等位基因进行额外的二次筛查可能会确定B*58:01携带者中别嘌呤醇诱导的DRESS风险进一步增加的人群。
UNASSIGNED: HLA-B*58:01 is a well-known risk factor for
allopurinol-induced severe cutaneous adverse reactions (SCARs). However, only a minority of HLA-B*58:01 carriers suffer SCARs after taking
allopurinol. The aim of this study was to investigate subsidiary genetic markers that could identify those at further increased risk of developing allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in subjects with HLA-B*58:01.
UNASSIGNED: Subjects with B*58:01 were enrolled (21
allopurinol-induced DRESS and 52
allopurinol-tolerant control). HLA-A, -B, -C and -DRB1 alleles were compared. Comparison of risk between HLAs and
allopurinol-induced SCAR in separate populations was performed to support the results. Kruskal-Wallis test, Pearson\'s chi-square test, Fisher\'s exact test and binary logistic regression were used to analyze the risk of SCAR development.
UNASSIGNED: Frequencies of A*24:02 (71.4 vs. 17.3%, p < 0.001, odds ratio [OR] = 12.0; 95% confidence interval [CI], 3.6-39.2) were significantly higher in B*58:01 (+) DRESS than B*58:01 (+) tolerant controls. In addition, DRB1*13:02 further increased the risk of DRESS. The phenotype frequency of A*24:02/DRB1*13:02 was significantly higher in the B*58:01 (+) DRESS group than in the B*58:01 (+) tolerant controls (52.4% vs. 5.8%, p < 0.001, OR, 66.0; 95% CI, 6.1-716.2). In 2782
allopurinol user cohort, the overall prevalence of DRESS was 0.22%, which increased to 1.62% and 2.86% in the presence of B*58:01 and B*58:01/A*24:02, respectively.
UNASSIGNED: The additional secondary screening with A*24:02 and DRB1*13:02 alleles may identify those at further increased risk of allopurinol-induced DRESS in B*58:01 carriers.