allele frequencies and implications for pharmacogenetics in the Kuwaiti population.

Unlabelled: 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.

Methods: 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.

Results: The distribution of alleles in the Kuwaiti population revealed that the most frequent alleles were HLA-B*50:01 (10.52%), HLA-B*51:01 (9.89%), HLA-B*08:01 (6.06%), HLA-B*52:01 (4.55%), HLA-B*18:01 (3.92%), and HLA-B*41:01 (3.65%). Notably, alleles HLA-B*13:01, HLA-B*13:02, HLA-B*15:02, HLA-B*15:13, HLA-B*35:02, HLA-B*35:05, HLA-B*38:01, HLA-B*40:02, HLA-B*44:03, HLA-B*51:01, HLA-B*57:01 and HLA-B*58:01 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.

Conclusion: 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.