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      Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population.

      International Journal of Dermatology

      Anticonvulsants, adverse effects, Asian Continental Ancestry Group, genetics, Carbamazepine, Genetic Markers, Genetic Predisposition to Disease, HLA-B Antigens, HLA-B15 Antigen, Humans, Incidence, Malaysia, epidemiology, Stevens-Johnson Syndrome, chemically induced, etiology

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          Carbamazepine (CBZ), a frequently used anticonvulsant drug, is one of the most common causes of life-threatening cutaneous adverse drug reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Recent studies have revealed a strong association between HLA-B*1502 and CBZ-induced TEN/SJS in the Taiwan Han Chinese population. This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population. A sample of 21 unrelated patients with CBZ-induced TEN/SJS and 300 race-matched, healthy controls were genotyped for HLA-A, -B and -DR using polymerase chain reaction (PCR). Allele frequencies were compared. HLA-B*1502 was present in 75.0% (12/16) of Malay patients with CBZ-induced TEN/SJS but in only 15.7% (47/300) of normal controls (odds ratio 16.15, 95% confidence interval 4.57-62.4; corrected P-value  = 7.87 × 10(-6) ), which suggests a strong association between HLA and CBZ-induced TEN/SJS. Additionally, HLA-B*1502 was found in all three Chinese and two Indian patients. Existing data show that frequencies of the HLA-B*1502 allele are generally much higher in Asian populations than in White European populations, which explains the higher incidences of SJS and TEN in Asian countries. HLA-B*1502 is strongly associated with CBZ-induced TEN/SJS in the Malay population in Malaysia, as has been seen in Han Chinese in Taiwan. This indicates that the genetic association apparent in the incidence of CBZ-induced TEN/SJS is linked with the presence of HLA-B*1502, irrespective of racial origin. Screening of patients for this genetic marker can help to prevent the occurrence of TEN/SJS. © 2011 The International Society of Dermatology.

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