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Genetic risk factors for antiepileptic drug–induced hypersensitivity reactions in Israeli populations
Authors:Shoshana Israel  Nicola Maggio  Dana Ekstein  Huda Zaid  Maria Firer  Yana Bederovsky  Iris Noyman  Revital Gandelman‐Marton  Ilan Blatt  Chaim Brautbar  Eli Marom  Dorit Nahlieli Dil  Erez Berman  David Sabag  Arieh Ingber  Sara Eyal
Affiliation:1. Tissue Typing Unit, Hadassah‐Hebrew University Medical Center, Jerusalem, Israel;2. Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel;3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;4. Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah‐Hebrew University Medical Center, Jerusalem, Israel;5. Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, Israel;6. Department of Pediatric Neurology, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel;7. Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel;8. Department of Pharmacology, Israel Ministry of Health, Jerusalem, Israel;9. Department of Dermatology, Hadassah‐Hebrew University Medical Center, Jerusalem, Israel
Abstract:The human leukocyte antigen (HLA) alleles B*15:02 and A*31:01 have been identified as predictive markers of adverse cutaneous effects of carbamazepine and phenytoin in Asian and North European populations, respectively. Our aim was to estimate the distribution of these alleles in Jewish and Arab populations in Israel. The HLA‐B*15:02 and HLA‐A*31:01 carrier rate was estimated based on data from the Hadassah Bone Marrow Registry. Data on Stevens‐Johnson syndrome (SJS)– and toxic epidermal necrolysis (TEN)–related hospitalizations were obtained from the Israeli Ministry of Health (MOH) registries and from four Israeli medical centers. Of 83,705 Jewish and Arab‐Muslim donors, 81 individuals of known origin carried the HLA‐B*15:02. Among them, 66 were Jews of India‐Cochin descent. Of the Cochin Jewish donors, 12.7% were B*15:02 carriers. HLA‐A*31:01 carrier incidence among Arab and Jewish Israeli populations (3.5% and 2.2%, respectively) was within the range reported in other countries. We did not identify SJS‐ or TEN‐related hospitalizations of Jews of Indian descent. Yet, this population should be considered at greater risk for antiepileptic drug–induced SJS and TEN. Until further data on actual risk are available, such patients should be typed for HLA‐B before treatment with carbamazepine or phenytoin.
Keywords:Stevens‐Johnson syndrome  HLA‐B*15:02  HLA‐A*31:01  Carbamazepine  Jewish  Arab‐Muslim
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