HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese.
Epilepsia
; 54(7): 1307-14, 2013 Jul.
Article
in En
| MEDLINE
| ID: mdl-23692434
ABSTRACT
PURPOSE:
HLA-B*1502 screening is recommended before starting carbamazepine in Han Chinese and Southeast Asians because the allele is strongly predictive of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) induced by the drug. We examined whether other HLA-B alleles are also involved and whether the association extends to other antiepileptic drugs (AEDs).METHODS:
Cases of SJS/TEN induced by any AEDs were recruited and matched (15) with AED-tolerant controls. Carrier rates of HLA-B alleles, determined by direct sequencing, were compared between cases and controls. Results were meta-analyzed with previous studies to examine the associations between HLA-B*1502 and SJS/TEN induced by phenytoin and lamotrigine. KEYFINDINGS:
A total of 55 cases (27 carbamazepine, 15 phenytoin, 6 lamotrigine, 7 other AEDs) and 275 controls were recruited. In drug-specific analysis, the carrier rate of HLA-B*1502 was significantly higher in carbamazepine-SJS/TEN cases compared with carbamazepine-tolerant controls (92.3% vs. 11.9%; p = 3.51 × 10(-18) ; odds ratio (OR) 89.25; 95% confidence interval (CI) 19.25-413.83), and also in phenytoin-SJS/TEN cases compared with phenytoin-tolerant controls (46.7% vs. 20.0%; p = 0.045; OR 3.50; 95% CI 1.10-11.18). Meta-analyses showed a strong association of HLA-B*1502 with phenytoin-SJS/TEN (p < 3 × 10(-4) ; OR 4.26; 95% CI 1.93-9.39) and, to a lesser extent, lamotrigine-SJS/TEN (p = 0.03; OR 3.59; 95% CI 1.15-11.22). Compared with drug-tolerant controls, the carrier rates of HLA-B*4001 and HLA-B*5801 were lower in cases of SJS/TEN induced by carbamazepine (p = 0.004) and other AEDs (p = 0.009), respectively.SIGNIFICANCE:
SJS/TEN induced by carbamazepine and phenytoin is strongly and moderately associated with HLA-B*1502 in Han Chinese, respectively. Possible protective associations with HLA-B*4001 and HLA-B*5801 warrant further investigation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin Diseases
/
HLA-B Antigens
/
Genetic Predisposition to Disease
/
Epilepsy
/
Anticonvulsants
Type of study:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limits:
Adolescent
/
Adult
/
Aged
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Epilepsia
Year:
2013
Type:
Article
Affiliation country:
China