Dashti Mohammed, Malik Md Zubbair, Al-Matrouk Abdullah, Bhatti Saeeda, Nizam Rasheeba, Jacob Sindhu, Al-Mulla Fahd, Thanaraj Thangavel Alphonse
Genetics and Bioinformatics Department, Dasman Diabetes Institute, Kuwait City, Kuwait.
Narcotic and Psychotropic Department, Ministry of Interior, Farwaniya, Kuwait.
Front Pharmacol. 2024 Oct 11;15:1423636. doi: 10.3389/fphar.2024.1423636. eCollection 2024.
This study explores the frequency of human leukocyte antigen (HLA) genes, particularly alleles, within the Kuwaiti population. We aim to identify alleles with known associations to adverse drug reactions (ADRs) based on existing literature. We focus on the gene due to its well-documented associations with severe cutaneous adverse reactions and the extensive pharmacogenetic research supporting its clinical relevance.
We utilized the HLA-HD tool to extract, annotate, and analyse alleles from the exome data of 561 Kuwaiti individuals, sequenced on the Illumina HiSeq platform. HLA typing was conducted using the HLA-HD tool with a reference panel from the IPD-IMGT/HLA database. The major pharmacogenetic markers were obtained from the HLA Adverse Drug Reaction Database, focusing on alleles with significant ADR associations in published literature.
The distribution of alleles in the Kuwaiti population revealed that the most frequent alleles were HLA-B50:01 (10.52%), HLA-B51:01 (9.89%), HLA-B08:01 (6.06%), HLA-B52:01 (4.55%), HLA-B18:01 (3.92%), and HLA-B41:01 (3.65%). Notably, alleles HLA-B13:01, HLA-B13:02, HLA-B15:02, HLA-B15:13, HLA-B35:02, HLA-B35:05, HLA-B38:01, HLA-B40:02, HLA-B44:03, HLA-B51:01, HLA-B57:01 and HLA-B58:01 were identified with known associations to various ADRs. For example, HLA-B*51:01 was associated with clindamycin, phenobarbital, and phenytoin, and was found in 18% of individuals.
Our study enriches the regional genetic landscape by delineating allele variations within Kuwait and across the Arabian Peninsula. This genetic insight, along with the identification of markers previously linked to drug hypersensitivity, provides a foundation for future pharmacogenetic research and potential personalized medicine strategies in the region.
本研究探讨了科威特人群中人类白细胞抗原（HLA）基因，特别是等位基因的频率。我们旨在根据现有文献确定与药物不良反应（ADR）有已知关联的等位基因。由于其与严重皮肤不良反应的关联有充分记录，且有广泛的药物遗传学研究支持其临床相关性，我们重点关注该基因。
我们利用HLA-HD工具从在Illumina HiSeq平台上测序的561名科威特个体的外显子组数据中提取、注释和分析等位基因。使用HLA-HD工具并参照IPD-IMGT/HLA数据库中的参考面板进行HLA分型。主要的药物遗传学标记从HLA药物不良反应数据库中获取，重点关注在已发表文献中有显著ADR关联的等位基因。
科威特人群中等位基因的分布显示，最常见的等位基因是HLA-B50:01（10.52%）、HLA-B51:01（9.89%）、HLA-B08:01（6.06%）、HLA-B52:01（4.55%）、HLA-B18:01（3.92%）和HLA-B41:01（3.65%）。值得注意的是，等位基因HLA-B13:01、HLA-B13:02、HLA-B15:02、HLA-B15:13、HLA-B35:02、HLA-B35:05、HLA-B38:01、HLA-B40:02、HLA-B44:03、HLA-B51:01、HLA-B57:01和HLA-B58:01被确定与各种ADR有已知关联。例如，HLA-B*51:01与克林霉素、苯巴比妥和苯妥英有关，在18%的个体中发现。
我们的研究通过描绘科威特境内及整个阿拉伯半岛的等位基因变异，丰富了区域遗传图谱。这种遗传见解，以及对先前与药物超敏反应相关的标记的识别，为该地区未来的药物遗传学研究和潜在的个性化医疗策略奠定了基础。
