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- Title
HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis.
- Authors
Genin, E; Chen, D-P; Hung, S-I; Sekula, P; Schumacher, M; Chang, P-Y; Tsai, S-H; Wu, T-L; Bellón, T; Tamouza, R; Fortier, C; Toubert, A; Charron, D; Hovnanian, A; Wolkenstein, P; Chung, W-H; Mockenhaupt, M; Roujeau, J-C
- Abstract
HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A*31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2-125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation.
- Subjects
HLA histocompatibility antigens; CARBAMAZEPINE; DRUG side effects; META-analysis; COST effectiveness; GENETIC determinism
- Publication
Pharmacogenomics Journal, 2014, Vol 14, Issue 3, p281
- ISSN
1470-269X
- Publication type
Article
- DOI
10.1038/tpj.2013.40