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HLA-B*1502 与卡马西平诱导的泰国人群严重皮肤不良反应的相关性。

Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population.

机构信息

Department of Pharmacology, Khon Kaen University, Khon Kaen, Thailand.

出版信息

Epilepsia. 2010 May;51(5):926-30. doi: 10.1111/j.1528-1167.2010.02533.x. Epub 2010 Mar 19.

Abstract

Carbamazepine (CBZ) has been reported as the most common culprit drug for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in several Asian countries including Thailand. A strong association between HLA-B1502 and CBZ-induced SJS/TEN has been reported in Han Chinese but not in Caucasian and Japanese populations. A case-control study was conducted to determine whether HLA-B1502 is a valid pharmacogenetic test for SJS/TEN caused by CBZ in a Thai population. Among 42 CBZ-induced patients with SJS/TEN, 37 (88.10%) patients carried the HLA-B1502 while only 5 (11.90%) of the CBZ-tolerant controls had this allele. The risk of CBZ-induced SJS/TEN was significantly higher in the patients with HLA-B1502, with an odds ratio (OR) of 54.76 [95% confidence interval (CI) 14.62-205.13, p = 2.89 x 10(-12)]. The sensitivity and specificity of HLA-B1502 for prediction of CBZ-induced SJS/TEN were 88.10%. By assuming a 0.27% as a prevalence rate of CBZ-induced SJS/TEN in a Thai population, the positive predictive value (PPV) and negative predictive value (NPV) of the HLA-B1502 were 1.92% and 99.96%. Results from this study suggest that HLA-B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ-induced SJS and TEN.

摘要

卡马西平(CBZ)已被报道为包括泰国在内的几个亚洲国家史蒂文斯-约翰逊综合征(SJS)和中毒性表皮坏死松解症(TEN)的最常见罪魁祸首药物。在汉族人群中,已经报道了 HLA-B1502 与 CBZ 诱导的 SJS/TEN 之间存在强烈关联,但在白种人和日本人中则没有。进行了一项病例对照研究,以确定 HLA-B1502 是否是泰国人群中由 CBZ 引起的 SJS/TEN 的有效药物遗传学检测。在 42 例 CBZ 诱导的 SJS/TEN 患者中,37 例(88.10%)患者携带 HLA-B1502,而仅 5 例(11.90%)CBZ 耐受对照者具有该等位基因。在携带 HLA-B1502 的患者中,CBZ 诱导的 SJS/TEN 的风险明显更高,其比值比(OR)为 54.76[95%置信区间(CI)14.62-205.13,p=2.89x10(-12)]。HLA-B1502 预测 CBZ 诱导的 SJS/TEN 的敏感性和特异性分别为 88.10%。假设泰国人群中 CBZ 诱导的 SJS/TEN 的患病率为 0.27%,则 HLA-B1502 的阳性预测值(PPV)和阴性预测值(NPV)分别为 1.92%和 99.96%。这项研究的结果表明,HLA-B*1502 可能是一种有用的药物遗传学检测方法,可用于筛选可能有风险的泰国个体发生 CBZ 诱导的 SJS 和 TEN。

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