HLA-A*02 alleles are associated with tetanus antitoxin-induced exanthematous drug eruptions in Chinese patients
HLA-A*02 alleles are associated with tetanus antitoxin-induced exanthematous drug eruptions in Chinese patients
复制标题
HLA-A02 等位基因与中国患者破伤风抗毒素引起的发疹性药疹相关。
DOI：
10.1097/fpc.0000000000000248
复制
发表时间：
2016-12-01
影响因子：
2.6
通讯作者：
Luo，Xiaoqun
中科院分区：
文献类型：
--
作者：
Yan，Sijia;Chen，Sheng-an;Luo，Xiaoqun
目的破伤风抗毒素（TAT）是一种有效的抗破伤风药物，但有时会引起药物不良反应，如速发性过敏性休克和迟发性皮肤不良反应，包括药疹（EDE）。人类白细胞抗原（HLA） I类等位基因与不同类型的皮肤药物不良反应密切相关。本研究旨在评估中国汉族人群中tat诱导的EDE与HLA-A、HLA-B和HLA-C等位基因之间是否存在关联。患者和方法我们对15例tat诱导的EDE患者和两组普通汉族患者进行了关联研究。采用pcr序列特异性寡核苷酸法测定每位患者HLA-A、HLA-B和HLA-C基因的等位基因水平基因型。结果tat诱导EDE患者HLA血清A2型携带者频率显著高于人类主要组织相容性复合体数据库中的汉族研究对象[n= 283，优势比(OR)= 6.93；P = 0.0061)。特别是HLA-A* 02: 01、HLA-A* 02: 06、HLA-A* 02: 07 3个A2等位基因的携带频率显著高于对照组（OR= 14.40； P= 2.4× 10−5）。HLA-B* 39: 01与HLA-A* 02: 06的连锁完全不平衡。因此，HLA-A* 02: 06/-B* 39: 01单倍型在病例和对照组的分布也有显著差异（OR= 105.00； P= 0.0024）。结论HLA-A* 02: 06/-B* 39: 01单倍型是tat诱导EDE的潜在遗传标记。此外，首次发现汉族人群中HLA-A2血清型，特别是A* 02: 01、A* 02: 06和A* 02: 07等位基因与tat诱导的EDE相关。
Objective Tetanus antitoxin (TAT) is an effective antitetanus medicine, but may sometimes cause adverse drug reactions such as rapid-onset anaphylactic shock and late-onset cutaneous adverse drug reactions, including exanthematous drug eruptions (EDE). Human leukocyte antigen (HLA) class I alleles are strongly associated with different types of cutaneous adverse drug reactions. This study aimed to assess whether there is an association between TAT-induced EDE and HLA-A, HLA-B, and HLA-C alleles in the Chinese Han population.Patients and methods We carried out an association study in 15 patients with TAT-induced EDE and two groups of general Han Chinese patients. Allele-level genotypes of the HLA-A, HLA-B, and HLA-C genes of each patient were determined using the PCR-sequence-specific oligonucleotides method.Results The carrier frequency of HLA serotype A2 was significantly higher in the TAT-induced EDE patients than in the general Han Chinese study participants from the human major histocompatibility complex database [n= 283, odds ratio (OR)= 6.93; P= 0.0061]. Particularly, the carrier frequency of three A2 alleles, including HLA-A* 02: 01, HLA-A* 02: 06, and HLA-A* 02: 07, is significantly higher than that of the control group (OR= 14.40; P= 2.4× 10− 5). Furthermore, HLA-B* 39: 01 was in complete linkage disequilibrium with HLA-A* 02: 06 in the case patients. Consequently, the distribution of the HLA-A* 02: 06/-B* 39: 01 haplotype was also significantly different in the cases and the controls (OR= 105.00; P= 0.0024).Conclusion The HLA-A* 02: 06/-B* 39: 01 haplotype is a potential genetic marker for the TAT-induced EDE. Furthermore, the HLA-A2 serotype, especially three alleles A* 02: 01, A* 02: 06, and A* 02: 07, was identified to be associated with the TAT-induced EDE in the Han Chinese population for the first time.