HLA-B38 and clozapine agranulocytosis in Israeli Jewish schizophrenia patients.
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文摘
It has been previously reported that clozapine induce agranulocytosis (agr) in Jewish patients possessing the haplotype HLA-B38\DR4. This haplotype is very common in Israel and about 10 % of Ashkenazi Israelis will be either B38\DR4 or B38\DR6. Hence it could be assumed that clozapine agr will be very common in Israel. This study was undertaken to exlore this issue and find whether the complication is associated also with HLAB38\DR6. About 1200 individuals have been treated with clozapine. The average daily dose was 150-300 mgr. and the precaution measures are those recommended by the manufacturer. However, due to the alertness of the physicians, even minor changes in white cell counts resulted in discontinuation of medication. It was found that ten patients developed agr. Nine patients were available for HLA typing. The results indicated that HLA B38 was present in 7 (77 % ). Class-II DNA typing revealed that four patients were DR4(two BRB1*0402 and 2 DRB1*0406) two were DR2(DRB1*1601) and one patient was DRB1*1302. One patient was typed as DRB1*0101\1101. Our results suggest that: Despite the fact that the susceptibility haplotype is frequent in Jews, the incidence of <b>agrb> is about 1 % which is similar to non-Jews. The heterogeneity of class-II associated antigens map the susceptibility gene closer to class-I, maybe to a class-III region gene.