Expressive

rs115384187 - CHI3L1 - CHIT1

Magnitude 4.5 · 1 study on file

Reported associations

  • Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. - Nature communications (2015) · Goldstein JI, Jarskog LF, Hilliard C, Alfirevic A, Duncan L, Fourches D, Huang H, Lek M, Neale BM, Ripke S, Shianna K, Szatkiewicz JP, Tropsha A, van den Oord EJ, Cascorbi I, Dettling M, Gazit E, Goff DC, Holden AL, Kelly DL, Malhotra AK, Nielsen J, Pirmohamed M, Rujescu D, Werge T, Levy DL, Josiassen RC, Kennedy JL, Lieberman JA, Daly MJ, Sullivan PF · PubMed 25187353

    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% confidence interval (CI)=0.12-0.29) and an amino acid change in the extracellular binding pocket of HLA-B (158T

Auto-generated from study metadata. AI-synthesised commentary is added when this entry is regenerated through content-service's LLM mode.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Bloodwork

  • white blood cell count during clozapine use Moderate

    CHI3L1 rs115384187-A carriers have elevated agranulocytosis risk on clozapine; intensive WBC monitoring can help prevent severe hematologic complications.

    If prescribed clozapine, maintain strict WBC monitoring per guidelines; consider more frequent baseline labs

Drug interactions

  • clozapine use and agranulocytosis risk Moderate

    CHI3L1 rs115384187-A is associated with 6.5x increased risk of clozapine-induced agranulocytosis, a potentially life-threatening hematologic side effect.

    Discuss variant status and alternative antipsychotics with psychiatrist before clozapine initiation