120. Benign Ethnic Neutropenia in a Sample of Nigerian Healthy Controls and Clozapine-Treated Schizophrenia Patients With DARC Null Variant

摘要

>Background: Benign ethnic neutropenia (BEN) is the occurrence of absolute neutrophil counts (ANC) of less than 1500 cells/mm³ observed in 10% to 30% of African and Middle Eastern ancestry individuals with no increased susceptibility to pyogenic infections. Recent evidence implicates polymorphism in the Duffy Antigen Receptor for Chemokines gene (DARC) in BEN persons of African descent. Until mid-2015 in the United States, the FDA clozapine treatment guidelines for ANC monitoring were based on normative ANC values in European ancestry populations without considerations for BEN. Compared with Caucasians, African Americans are less likely to be initiated on clozapine and their treatment twice as likely to be discontinued for neutropenia. Gathering data indicate no increased agranulocytosis risk in clozapine-treated BEN individuals. Advancing knowledge of BEN pathophysiology could reduce a substantial barrier to clozapine treatment in African-American patients. >Methods: We examined ANC data collected on a sample of 136 schizophrenia and 33 healthy control Yoruba participants recruited at the Federal Neuropsychiatric Hospital Yaba, Lagos. Exclusion criteria included medical conditions that could affect white blood cell counts. In the patient group, 100 had been on stable clozapine treatment (>6 months). In a subgroup of participants (n = 69), we assayed the regulatory variant (rs2814778) in the promoter of DARC (DARC -46T > C) implicated in low neutrophil counts in African-ancestry populations. >Results: The sample consisted of 88 females and 81 males. Sex was not different between schizophrenia and control groups (P = .3). Age differed between schizophrenia (mean [SD], 40.15 [13.15] years) and controls (mean [SD], 29.12 [5.08] years; P < .001). The sample mean ANC was 2,557/mm3 (range 800 to 6,970); with 31% and 11% showing ANC below 2000 and 1500/mm³, respectively. The mean daily clozapine dose was 224 mg. Clozapine-treated patients had a significantly higher mean ANC (2777/mm³ [0.97]) compared with controls and non-clozapine treated patients (2238/mm³ [0.88]; P < .001). All 69 individuals assayed for rs2814778 were homozygous for the Duffy-null allele (DARC -46T > C). >Conclusion: The results are consistent with reported rates of BEN in African populations, supports the safety of clozapine monitoring using lower ANC levels in BEN populations, and demonstrates the common occurrence of the African-derived “null” DARC gene variant in this sample.