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HLA-B 等位基因与拉莫三嗪在中国汉族人群中的皮肤不良反应。

Hla-B alleles and lamotrigine-induced cutaneous adverse drug reactions in the Han Chinese population.

机构信息

Institute of Neuroscience and Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and Ministry of Education of China, Guangzhou, China.

出版信息

Basic Clin Pharmacol Toxicol. 2011 Jul;109(1):42-6. doi: 10.1111/j.1742-7843.2011.00681.x. Epub 2011 Mar 16.

Abstract

Lamotrigine (LTG) is a commonly used antiepileptic drug. However, the use of LTG is limited because of its cutaneous adverse drug reactions (cADRs) ranging from mild maculopapular eruption (MPE) to severe Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between HLA-B1502 and carbamazepine-induced SJS/TEN has been identified in Chinese and Thai. Although three of seven cases with HLA-B1502 have been reported in LTG-induced SJS/TEN so far, the relationship between HLA-B1502 and LTG-induced SJS/TEN needs further investigation. It is also unclear whether there is a specific genetic marker associated with LTG-induced MPE in Chinese. In this study, we genotyped 43 Han Chinese patients treated with LTG (14 cases with LTG-induced cADRs and 29 LTG-tolerant controls), using PCR-SSP for HLA-B1502 testing and low-resolution genotyping, as well as sequencing for four-digit genotyping. The two cases with SJS were negative for HLA-B1502, with B1301/1301 and 4601/5610, respectively. Combining the data with previous studies, there was no significant difference in the frequency of subjects with HLA-B1502 between the LTG-induced SJS/TEN group and the LTG-tolerant group (p = 0.08, OR 4.23, 95% CI 0.94-18.97). In the MPE group, only one was positive for HLA-B1502. There was no significant difference in the frequency of a specific HLA-B allele between the MPE group and the LTG-tolerant group either. In this study, no significant association between HLA-B1502 and LTG-induced SJS or MPE was found. Given the small sample size and only HLA-B locus genotyping, further large-scale studies are required to explore genetic associations with LTG-induced cADRs.

摘要

拉莫三嗪(LTG)是一种常用的抗癫痫药物。然而,由于其皮肤不良反应(cADR)范围从轻度斑丘疹疹(MPE)到严重的史蒂文斯-约翰逊综合征(SJS)和中毒性表皮坏死松解症(TEN),LTG 的使用受到限制。在中国和泰国,已经确定 HLA-B1502 与卡马西平诱导的 SJS/TEN 之间存在强烈关联。尽管迄今为止已有 7 例与 HLA-B1502 相关的 LTG 诱导的 SJS/TEN 报道,但 HLA-B1502 与 LTG 诱导的 SJS/TEN 之间的关系仍需进一步研究。目前尚不清楚在中国,是否存在与 LTG 诱导的 MPE 相关的特定遗传标记。在这项研究中,我们对 43 名接受 LTG 治疗的汉族患者进行了基因分型(14 例为 LTG 诱导的 cADR,29 例为 LTG 耐受对照),使用 PCR-SSP 进行 HLA-B1502 检测和低分辨率基因分型,以及测序进行四位数字基因分型。两名 SJS 患者的 HLA-B1502 检测结果均为阴性,分别为 B1301/1301 和 4601/5610。将数据与以前的研究相结合,LTG 诱导的 SJS/TEN 组与 LTG 耐受组之间 HLA-B1502 出现的频率没有显著差异(p=0.08,OR 4.23,95%CI 0.94-18.97)。在 MPE 组中,只有一名患者的 HLA-B1502 检测结果为阳性。MPE 组与 LTG 耐受组之间 HLA-B 等位基因的出现频率也没有显著差异。在这项研究中,未发现 HLA-B1502 与 LTG 诱导的 SJS 或 MPE 之间存在显著关联。由于样本量较小且仅进行了 HLA-B 基因座基因分型,因此需要进一步进行大规模研究以探讨与 LTG 诱导的 cADR 相关的遗传关联。

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