HLA Pharmacogenetic Markers of Drug Hypersensitivity in a Thai Population.
HLA Pharmacogenetic Markers of Drug Hypersensitivity in a Thai Population.
复制标题
DOI：
10.3389/fgene.2018.00277
复制
发表时间：
2018
影响因子：
3.7
通讯作者：
Tassaneeyakul W
中科院分区：
文献类型：
--
作者：
Nakkam N;Konyoung P;Kanjanawart S;Saksit N;Kongpan T;Khaeso K;Khunarkornsiri U;Dornsena A;Tassaneeyakul W;Tassaneeyakul W
重度皮肤药物不良反应（SCAR）包括Stevens-Johnson综合征（SJS）、中毒性表皮坏死松解症（TEN）和伴有嗜酸性粒细胞增多和全身症状的药物反应（DRESS），是由多种药物引起的可能危及生命的皮肤反应。最近，一些编码人类抗原呈递蛋白（HLA等位基因）的基因被发现是预测这些危及生命的反应的有效药物遗传学标记。本研究的目的是确定HLA等位基因的分布，包括HLA I类和II类基因在183个无关的个体的泰国人口使用高分辨率HLA基因分型，以获得2场数据（4位数分辨率），并比较频率的HLA等位基因，已提出作为标记的SCAR与其他种族。结果显示，药物诱导的SCAR的药物遗传学标志物的患病率较高，B*13：01为氨苯砜;卡马西平和奥卡西平的B*15：02;别嘌呤醇的B*58：01、A*33：03和C*03：02;复方新诺明的C*08：01、C*14：02和DRB 1 *12：02。阿巴卡韦B*57：01和苯妥英B *56：02/B* 56：04引起的SCAR的药物遗传学标志物的发生率较低。泰国人群中观察到的B*13：01、B*15：02和B*58：01等位基因频率显著高于日本和高加索人群中报告的频率。与在其他东南亚人群中观察到的相似，在研究人群中观察到A*31：01和B*57：01等位基因的低频率。基于HLA药物遗传学标记的频率，泰国和其他东南亚人群与高加索人群相比可能处于更高的药物诱导的SCAR风险。
Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS) are potentially life-threatening cutaneous reactions caused by several drugs. Recently, a number of genes encoding for human antigen presenting proteins, HLA alleles, have been discovered as valid pharmacogenetic markers for prediction of these life-threatening reactions. This study was aimed to determine the distribution of HLA alleles including the HLA class I and class II genes in 183 unrelated individuals of a Thai population using high resolution HLA genotyping in order to obtain 2-field data (4-digit resolution) and compare the frequencies of the HLA alleles that have been proposed as markers of SCARs with other ethnics. Results revealed a high prevalence of pharmacogenetic markers of drug-induced SCARs e.g., B*13:01 for dapsone; B*15:02 for carbamazepine and oxcarbazepine; B*58:01, A*33:03 and C*03:02 for allopurinol; C*08:01, C*14:02 and DRB1*12:02 for co-trimoxazole. Whereas, low prevalence of pharmacogenetic markers of SCARs induced by abacavir, B*57:01 and phenytoin, B*56:02/B*56:04 were noticed. The allele frequencies of B*13:01, B*15:02, and B*58:01 observed in a Thai population were significantly higher than those reported in Japanese and Caucasian populations. Similar to those observed in other Southeast Asian populations, low frequencies of A*31:01 and B*57:01 alleles were noted in the study population. Based on the frequencies of HLA pharmacogenetic markers, Thai and other Southeast Asian populations may at higher risk of drug-induced SCARs compared with Caucasian population.