Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Department of Pharmacy, College of Pharmacy, University of the Philippines Manila, Manila, Philippines.
Pharmacogenomics J. 2020 Jun;20(3):533-541. doi: 10.1038/s41397-019-0143-8. Epub 2020 Jan 3.
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.
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。