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


OBJECTIVE
This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Dermatology, Kuala Lumpur Hospital Allergy and Immunology Research Center, Kuala Lumpur, Malaysia. ccchor@gmail.com
Choong-Chor
CC
Chang
Chun-Lai
CL
Too
Shahnaz
S
Murad
Suraiya Hani
SH
Hussein
D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D002220:Carbamazepine / Q000009:adverse effects*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics*; D059910:HLA-B15 Antigen; D006801:Humans; D015994:Incidence; D008296:Malaysia / Q000453:epidemiology; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*
D000927:Anticonvulsants; D005819:Genetic Markers; D015235:HLA-B Antigens; C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen; D002220:Carbamazepine