rs116688600 - CCNB3P1 - CDH9
Magnitude 4.5 · 1 study on file
Reported associations
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Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles - Unknown journal (n.d.) · Unknown authors · PubMed 25187353
ABSTRACT: Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perform the largest and most comprehensive genetic study of CIAG to date by interrogating 163 cases using genome-wide genotyping and whole-exome sequencing. We find that two loci in the major histocompatibility complex are independently associated with CIAG: a single amino acid in HLA-DQB1 (126Q) (P=4.7×10−14, odds ratio, OR=0.19, 95% CI 0.12-0.29) and an amino acid change in the extracellular binding pocket of HLA-B (158T) (P=6.4×10
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Lifestyle context
Concrete actions anchored to the cited research. We do not prescribe, we describe.
Discuss with your doctor
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clozapine-induced agranulocytosis risk Moderate
Carriers of rs116688600 C allele have approximately 5-fold increased risk of clozapine-induced agranulocytosis, a potentially life-threatening hematologic adverse effect.
If taking or considering clozapine, discuss with prescribing physician and establish WBC monitoring