HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis
| Autor: | Dominique Charron, Fortier C, Teresa Bellón, Ryad Tamouza, Shuen-Iu Hung, Maja Mockenhaupt, Wolkenstein P, Jean-Claude Roujeau, Emmanuelle Génin, Chang Py, Wen-Hung Chung, Alain Hovnanian, Antoine Toubert, Martin Schumacher, Chen Dp, Tsai Sh, Wu Tl, Peggy Sekula |
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| Rok vydání: | 2013 |
| Předmět: |
Pharmacology
HLA-A Antigens business.industry education Genomics macromolecular substances Carbamazepine Bioinformatics Proteomics HLA-A Cohort Studies Drug development Meta-analysis Genetics Humans Molecular Medicine Medicine business Functional genomics health care economics and organizations Skin medicine.drug |
| Zdroj: | The Pharmacogenomics Journal. 14:281-288 |
| ISSN: | 1473-1150 1470-269X |
| DOI: | 10.1038/tpj.2013.40 |
| Popis: | 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 (P0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P0.001; 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 (P0.001, 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 (P0.001, 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. |
| Databáze: | OpenAIRE |
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