PMID- 11266078
OWN - NLM
STAT- MEDLINE
DCOM- 20010614
LR  - 20191025
IS  - 0960-314X (Print)
IS  - 0960-314X (Linking)
VI  - 11
IP  - 2
DP  - 2001 Mar
TI  - Further evidence of human leukocyte antigen-encoded susceptibility to 
      clozapine-induced agranulocytosis independent of ancestry.
PG  - 135-41
AB  - To further examine the human leukocyte antigen (HLA)-encoded genetic 
      susceptibility to clozapine-induced agranulocytosis (CA) we performed 
      HLA-genotyping in a sample of German schizophrenic patients, who suffered from 
      this haematotoxic side-effect. Thirty-one schizophrenic patients with CA (17 
      women and 14 men) and 77 schizophrenic comparison subjects (40 women and 37 men) 
      were included in the study. HLA-genotyping included identification of major 
      histocompatibility complex (MHC) class I (HLA-A, B, Cw) and class II (HLA-DR, DQ) 
      antigens. CA was significantly associated with HLA-Cw*7 (P<0.02), DQB*0502 
      (P<0.04), DRB1*0101 (P<0.03) and DRB3*0202 (P<0.02). These HLA-haplotypes are 
      also partly linked to other diseases with a strong genetic background. All other 
      antigens revealed no association to this haematotoxic reaction. In addition, we 
      did not find gender-related effects, whereas age seemed to be a further major 
      risk factor of CA (P<0.0003). Thus, HLA loci may serve as genetic marker to 
      identify subjects of different ethnic subgroups prone to this severe 
      idiosyncratic drug reaction of clozapine. Further studies are needed to 
      investigate whether these associations with CA are due to causal involvement or 
      linkage disequilibrium.
FAU - Dettling, M
AU  - Dettling M
AD  - Department of Psychiatry, University Hospital Benjamin Franklin, Free University 
      of Berlin, Germany. michael.dettling@charite.de
FAU - Schaub, R T
AU  - Schaub RT
FAU - Mueller-Oerlinghausen, B
AU  - Mueller-Oerlinghausen B
FAU - Roots, I
AU  - Roots I
FAU - Cascorbi, I
AU  - Cascorbi I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Pharmacogenetics
JT  - Pharmacogenetics
JID - 9211735
RN  - 0 (Antipsychotic Agents)
RN  - 0 (HLA Antigens)
RN  - J60AR2IKIC (Clozapine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Agranulocytosis/*chemically induced/*genetics
MH  - Antipsychotic Agents/*adverse effects/therapeutic use
MH  - Case-Control Studies
MH  - Clozapine/*adverse effects/therapeutic use
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Schizophrenia/*drug therapy
EDAT- 2001/03/27 10:00
MHDA- 2001/06/23 10:01
CRDT- 2001/03/27 10:00
PHST- 2001/03/27 10:00 [pubmed]
PHST- 2001/06/23 10:01 [medline]
PHST- 2001/03/27 10:00 [entrez]
AID - 10.1097/00008571-200103000-00004 [doi]
PST - ppublish
SO  - Pharmacogenetics. 2001 Mar;11(2):135-41. doi: 10.1097/00008571-200103000-00004.