Investigation of the Prevalence of the HLA-B*15:02 Allele in the Asian Populations: A Comprehensive Analysis Through...

The HLA-B*15:02 allele is related to a high risk of severe cutaneous adverse drug reactions (SCARs) in patients taking certain antiepileptic drugs. However, its prevalence in the Asian population and the number of drugs linked to SCARs due to the carriage of this variant are relatively underexplored. This study sought to address these knowledge gaps.

The prevalence of the HLA-B*15:02 allele in Asian populations was estimated by using the data from the Allele Frequency Net Database. Weighted means, standard deviations, and 95% Confidence Interval (CI) were estimated for the study populations, and the chi-square test was used to assess the statistical significance of variability in allele frequencies across populations. Drugs associated with SCARs due to HLA-B*15:02 were identified from the clinical guidelines of the international pharmacogenomics (PGx) working groups.

HLA-B*15:02 was most prevalent in South-East Asia (5.6% ± 3.1), followed by South Asia (2.1% ± 1.5), North-East Asia (0.6% ± 0.9), and West Asia (0.01% ± 0.05). This distribution was statistically significant (χ² = 9712.5, df = 3, p < 0.001; χ ² test). Country-wise, prevalence was the highest in the Philippines (22%; 95% CI, 11.53-35.96%), followed by Vietnam (13.5%; 95% CI, 8.77-19.61%), Indonesia (11.9% ± 1.5), Malaysia (10% ± 4.3), Hong Kong (9.3% ± 0.2), Thailand (8.4% ± 0.1), Singapore (8.1% ± 3.7), China (5.4% ± 5.4), Taiwan (4.4% ± 0.7), Sri Lanka (2.5%, single study), India (2.1% ± 1.5) and South Korea (1.5% ± 0.9). PharmGKB clinical annotations identified four drugs (carbamazepine, oxcarbazepine, lamotrigine, phenytoin) with strong evidence (Level 1 A) for HLA-B*15:02-related SCARs, though the majority of the evidence for lamotrigine came from the Han Chinese Population. International PGx working groups require or recommend preemptive HLA-B*15:02 genotyping for at least three drugs, i.e., carbamazepine, oxcarbazepine, and phenytoin.

Considering the high prevalence of the HLA-B*15:02 in the Southeast and South Asians, and its association with drug-induced SCARs, pre-emptive HLA-B*15:02 testing may reduce SCARs substantially in this region.