A patient on clozapine develops severe agranulocytosis. The pharmacogenomic marker most strongly associated with clozapine-induced agranulocytosis in Caucasians is:

• A HLA-B*57:01 allele
• B CYP1A2 ultrarapid metabolizer phenotype
• C G6PD deficiency leading to oxidative marrow stress
• D HLA-DQB1*02 and HLA-B*38 alleles ✓

Explanation

HLA-DQB1*02 and HLA-B*38 alleles have been identified as strong genetic predictors of clozapine-induced agranulocytosis in Caucasian populations through pharmacogenomic studies. HLA-B*57:01 is associated with abacavir hypersensitivity, not clozapine toxicity. CYP1A2 activity affects clozapine plasma levels (smokers have higher enzyme activity and may need higher doses) but does not directly predict agranulocytosis. G6PD deficiency causes hemolytic anemia with oxidizing drugs but is unrelated to clozapine-induced granulocyte depletion.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.