HLA‐B*15:02 association with carbamazepine‐induced Stevens‐Johnson syndrome and toxic epidermal necrolysis in an Indian population: a pooled‐data analysis and meta‐analysis

This study aimed to investigate the prevalence and association of HLA‐B*15:02 with carbamazepine‐induced Stevens‐Johnson syndrome and toxic epidermal necrolysis (CBZ‐SJS/TEN) in the Indian population in Malaysia, which mostly originated from Southern India. HLA‐B alleles in five Indian case patients with CBZ‐SJS/TEN and 52 CBZ‐tolerant controls, and followed by a pooled sample of seven cases from two centers in Malaysia were analyzed. Positive association for HLA‐B*15:02 with CBZ‐SJS/TEN was detected in Indians (40% [2/5] vs. 3.8% [2/52], odds ratio [OR] 16.7, p = 0.0349), of which 80% (4/5) of the Indian patients originated from Southern India. A pooled sample of seven cases showed stronger association between HLA‐B*15:02 and CBZ‐SJS/TEN (57.1% [4/7] vs. 3.8% [2/52], OR 33.3, 95% confidence interval [CI] 4.25–162.21, p = 1.05 × 10^?3). Subsequent meta‐analysis on Indians from Malaysia and India further demonstrated a significant and strong association between HLA‐B*15:02 and CBZ‐SJS/TEN (OR 38.54; 95% CI 6.83–217.34, p < 1.0 × 10^?4). Our study is the first on Indians predominantly from Southern India that demonstrated HLA‐B*15:02 as a strong risk factor for CBZ‐SJS/TEN despite a low population allele frequency. This stressed the importance of testing for HLA‐B*15:02, irrespective of the ancestral background, including populations with low allele frequency.