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菲律宾患者中卡马西平诱导的史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症与 HLA-B75 血清型或 HLA-B*15:21 等位基因的关联。

Association of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis with the HLA-B75 serotype or HLA-B*15:21 allele in Filipino patients.

机构信息

Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

Department of Pharmacy, College of Pharmacy, University of the Philippines Manila, Manila, Philippines.

出版信息

Pharmacogenomics J. 2020 Jun;20(3):533-541. doi: 10.1038/s41397-019-0143-8. Epub 2020 Jan 3.

Abstract

A case-control study was conducted to investigate the association of HLA-A alleles, HLA-B alleles including HLA-B15:02 and HLA-B75 serotype with carbamazepine-induced SJS/TEN in Filipino patients. A retrospective review of medical records was performed. Pertinent clinical data were collected. Eight (8) carbamazepine-induced SJS/TEN cases and 32 tolerant controls were recruited. Genomic DNA was extracted from the saliva samples and genotyping was performed by employing allele-specific polymerase chain reaction. Data were analyzed using the Fisher's exact test, Mann-Whitney U test, univariate logistic regression, and multivariate logistic regression. Single allele association analysis was done. The strength of association was expressed as odds ratio with 95% confidence interval. Positive predictive value, negative predictive value, sensitivity, and specificity were computed. Of all the alleles tested, the HLA-B75 serotype (p = 0.007, OR = 23.25, 95% CI = 2.33-232.21) and HLA-B15:21 (p = 0.026, OR = 7.53, 95% CI = 1.27-44.79) were significantly associated with carbamazepine-induced SJS/TEN. The HLA-B75 serotype or HLA-B*15:21 allele may be used as a genetic risk assessment prior to prescription for prevention of carbamazepine-induced SJS/TEN in Filipino patients.

摘要

一项病例对照研究旨在调查 HLA-A 等位基因、HLA-B 等位基因(包括 HLA-B15:02 和 HLA-B75 血清型)与菲律宾患者卡马西平诱导的 SJS/TEN 之间的关联。对病历进行了回顾性审查。收集了相关的临床数据。招募了 8 例卡马西平诱导的 SJS/TEN 病例和 32 例耐受对照。从唾液样本中提取基因组 DNA,并通过等位基因特异性聚合酶链反应进行基因分型。使用 Fisher's 确切检验、Mann-Whitney U 检验、单变量逻辑回归和多变量逻辑回归分析数据。进行了单等位基因关联分析。关联的强度表示为优势比及其 95%置信区间。计算了阳性预测值、阴性预测值、敏感性和特异性。在所有测试的等位基因中,HLA-B75 血清型(p=0.007,OR=23.25,95%CI=2.33-232.21)和 HLA-B15:21(p=0.026,OR=7.53,95%CI=1.27-44.79)与卡马西平诱导的 SJS/TEN 显著相关。HLA-B75 血清型或 HLA-B*15:21 等位基因可用于菲律宾患者卡马西平诱导的 SJS/TEN 预防前的遗传风险评估。

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