Expressive

rs114397494 - XRCC4

Magnitude 4.5 · 1 study on file

Reported associations

  • 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.

Bloodwork

  • white blood cell count during clozapine therapy Moderate

    rs114397494 variant confers 2.96-fold increased agranulocytosis risk with clozapine; early WBC decline detection prevents critical myelosuppression

    Baseline WBC check before starting; then monitor per clozapine protocol

Discuss with your doctor

  • clozapine agranulocytosis risk before initiation Moderate

    rs114397494 in XRCC4 associated with 2.96-fold increased clozapine-induced agranulocytosis risk via impaired immune cell DNA repair

    Inform prescriber of genetic risk if clozapine is being considered

Drug interactions

  • alternative antipsychotics to clozapine Moderate

    rs114397494 increases agranulocytosis risk with clozapine; alternatives may be safer depending on clinical indication

    If clozapine is being considered, discuss alternative antipsychotics with prescriber