HLA-B Alleles and Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Han Chinese Population
HLA-B Alleles and Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Han Chinese Population
复制标题
中国汉族人群 HLA-B 等位基因与拉莫三嗪引起的皮肤药物不良反应
DOI：
10.1111/j.1742-7843.2011.00681.x
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发表时间：
2011-07-01
影响因子：
3.1
通讯作者：
Liao, Wei-Ping
中科院分区：
文献类型：
--
作者：
Shi, Yi-Wu;Min, Fu-Li;Liao, Wei-Ping
拉莫三嗪(LTG)是常用的抗癫痫药物。然而，LTG的使用受到限制，因为它的皮肤不良反应(CADR)范围从轻度黄斑丘疹(MPE)到重度Stevens Johnson综合征(SJS)和中毒性表皮坏死松解症(TEN)。在中国人和泰国人中，已发现人类白细胞抗原-B*1502与卡马西平诱导的SJS/TEN有很强的相关性。虽然到目前为止，在LTG诱导的SJS/TEN中已报道了7例中3例携带HLAB*1502，但HLAB*1502与LTG诱导的SJS/TEN的关系仍需进一步研究。目前也不清楚是否存在与LTG诱导的中国人MPE相关的特定遗传标记。在这项研究中，我们对43例接受LTG治疗的汉族患者(14例LTG诱导的cADR和29例LTG耐受对照)进行了基因分型，并采用聚合酶链式反应-序列分析(PCR-SSP)进行了人类白细胞抗原-B*1502检测和低分辨率基因分型，以及四位数基因分型测序。两例SJS患者的HLAB*1502均为阴性，分别为B1301/1301和4601/5610。结合以往的研究，LTG诱导的SJS/TEN组和LTG耐受组的HLAB*1502基因频率无显著差异(P=0.08，OR 4.23，95%CI 0.94~18.97)。在MPE组中，仅1例HLAB*1502阳性。在MPE组和LTG耐受组之间，特定的HLA-B等位基因频率也没有显著差异。在本研究中，未发现HLAB*1502与LTG诱导的SJS或MPE显著相关。考虑到样本量较小，而且只有HLA-B基因分型，需要进一步的大规模研究来探索与LTG诱导的cADRs的遗传关联。
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-B*1502 and carbamazepine-induced SJS/TEN has been identified in Chinese and Thai. Although three of seven cases with HLA-B*1502 have been reported in LTG-induced SJS/TEN so far, the relationship between HLA-B*1502 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-B*1502 testing and low-resolution genotyping, as well as sequencing for four-digit genotyping. The two cases with SJS were negative for HLA-B*1502, 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-B*1502 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-B*1502. 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-B*1502 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.