Abstract

Background: HLA-A gene is one of the most polymorphic loci in human genome and its variants influence disease susceptibility and immune checkpoint inhibitor (ICI) therapy response. HLA-A*03 allele has been identified as a biomarker associated with poor ICI response. Objective: This study aimed to characterize HLA-A allele and genotype frequencies in the Bosnian population, assess sex specific differences, and evaluate the prevalence of HLA-A*03. Methods: Blood samples from 75 individuals were analyzed. Genomic DNA was isolated using the Miller method, and HLA-A typing was performed using PCR with sequence specific primers (PCR-SSP). Polymorphism parameters were calculated using PowerMarker v3.25. Differences between males and females were assessed using chi square and Fisher’s exact tests. Results: Twelve HLA-A allelic groups and 28 genotypes were identified. The most frequent alleles were HLA-A*02 (33.33%), A*01 (16.67%), A*24 (11.33%), A*03 (10%), and A*11 (8%). The most common genotypes were HLA-A*01/*02 (12%), A*02/*02 (12%), and A*02/*03 (8%). Females showed significantly higher frequencies of HLA-A*02, A*03, and A*31, as well as genotypes HLA-A*02/*03, A*02/*11, and A*02/*31. The population exhibited high polymorphism (heterozygosity 0.8667; gene diversity 0.8232; PIC 0.8054). Strong similarity with European and Western groups and substantial divergence from East Asian and African populations were detected. Conclusion: The Bosnian population demonstrates high HLA-A polymorphism, with HLA-A*02 as the most common allele. Females more frequently carry the HLA-A*03 allele and several related genotypes, suggesting potential sex specific implications for ICI therapy response. These findings provide a foundation for future studies investigating the clinical relevance of HLA-A variation in Bosnian cancer patients undergoing immunotherapy.

Key words: HLA-A gene, Bosnian population, allele frequency, PCR-SSP