title: 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.
abstract: 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.
authors.affiliation: Division of Neurology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Genetics and Molecular Biology Unit, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Amy Hui-Ping
authors.initials: AH
authors.lastname: Khor
authors.forename: Kheng-Seang
authors.initials: KS
authors.lastname: Lim
authors.forename: Chong-Tin
authors.initials: CT
authors.lastname: Tan
authors.forename: Su-Ming
authors.initials: SM
authors.lastname: Wong
authors.forename: Ching-Ching
authors.initials: CC
authors.lastname: Ng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002220:Carbamazepine / Q000494:pharmacology*; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D059910:HLA-B15 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000276:immunology; D012307:Risk Factors; D013262:Stevens-Johnson Syndrome / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
chemical_list: D059910:HLA-B15 Antigen; D002220:Carbamazepine
keywords: Carbamazepine; HLA-B*15:02; Indian; Malaysia; Steven-Johnson syndrome