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Pharmacogenomics J. 2014 Jun;14(3):281-8. doi: 10.1038/tpj.2013.40. Epub 2013 Dec 10.

HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis.

Author information

1
Inserm U946, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
2
1] Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Department of Medical Biotechnology and Laboratory Science, Chang Gung University College of Medicine, Taoyuan, Taiwan.
3
Institute of Pharmacology, School of Medicine, Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan.
4
Institute of Medical Biometry and Medical Informatics, Freiburg University-Medical Center, Freiburg, Germany.
5
Research Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
6
1] Jean Dausset Laboratory, Saint Louis Hospital, Paris, France [2] Inserm UMRS 940, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
7
Inserm UMRS 940, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
8
Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Keelung, Linko, Chang Gung University College of Medicine, Taipei, Taiwan.
9
Dokumentationszentrum schwerer Hautreaktionen (dZh), Department of Dermatology, Freiburg University-Medical Center, Freiburg, Germany.
10
Service Dermatologie, Hôpital Henri-Mondor, Université Paris-Est, Créteil, France.

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.

PMID:
24322785
DOI:
10.1038/tpj.2013.40
[Indexed for MEDLINE]
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