title: Genetic risk factors for antiepileptic drug-induced hypersensitivity reactions in Israeli populations.
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.
authors.affiliation: Tissue Typing Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Shoshana
authors.initials: S
authors.lastname: Israel
authors.affiliation: Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Nicola
authors.initials: N
authors.lastname: Maggio
authors.affiliation: Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Ekstein
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, Israel.
authors.forename: Huda
authors.initials: H
authors.lastname: Zaid
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, Israel.
authors.forename: Maria
authors.initials: M
authors.lastname: Firer
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, Israel.
authors.forename: Yana
authors.initials: Y
authors.lastname: Bederovsky
authors.affiliation: Department of Pediatric Neurology, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Noyman
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel.
authors.forename: Revital
authors.initials: R
authors.lastname: Gandelman-Marton
authors.affiliation: Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Blatt
authors.affiliation: Tissue Typing Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Chaim
authors.initials: C
authors.lastname: Brautbar
authors.affiliation: Department of Pharmacology, Israel Ministry of Health, Jerusalem, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Marom
authors.affiliation: Department of Pharmacology, Israel Ministry of Health, Jerusalem, Israel.
authors.forename: Dorit
authors.initials: D
authors.lastname: Nahlieli Dil
authors.affiliation: Department of Pharmacology, Israel Ministry of Health, Jerusalem, Israel.
authors.forename: Erez
authors.initials: E
authors.lastname: Berman
authors.affiliation: Tissue Typing Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Sabag
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Arieh
authors.initials: A
authors.lastname: Ingber
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, Israel. sarae@ekmd.huji.ac.il.
authors.forename: Sara
authors.initials: S
authors.lastname: Eyal
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects*; D018912:Arabs; D004342:Drug Hypersensitivity / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology* / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007557:Israel / Q000453:epidemiology / Q000208:ethnology; D007585:Jews; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000927:Anticonvulsants; D015234:HLA-A Antigens; D015235:HLA-B Antigens
keywords: Arab-Muslim; Carbamazepine; HLA-A*31:01; HLA-B*15:02; Jewish; Stevens-Johnson syndrome