Analysis of Flavin-Containing Monooxygenase 3 Genotype Data in Populations Administered the Anti-Schizophrenia Agent Olanzapine

John   R.   Cashman; Jun      Zhang; Matthew   R.   Nelson; Andreas      Braun

Abstract

Flavin-containing monooxygenase 3 (FMO3) genotype data for European-, Latin-, African- and Asian- American schizophrenia patients administered olanzapine were compared to age-, gender-, and race/ethnicity-matched controls. Single nucleotide polymorphisms and haplotypes associated with case-control status was undertaken to determine the potential role of FMO3 in olanzapine therapeutic response. The relationship between side effects and FMO3 genotype and allele frequencies was also studied. For European Americans, significant differences in individual cases versus controls were observed between FMO3 158 and 257 alleles and genotype frequencies and schizophrenia delusions, hallucinations, and weight gain/increased appetite but this was not observed in a replicated population. For Latin Americans, a significant difference in individual cases versus controls was observed for FMO3 158 and 257 for schizophrenia delusions as well as hallucinations and delusions. Sleepiness and weight gain was associated with allele 308. In African Americans, a comparison of allele frequency and diagnosis showed a significant dependence on allele 158 in individual cases versus controls. FMO3 genotype and allele frequency was not significantly associated with auditory hallucinations or delusions. For Asian Americans, no significant difference in allele or genotype frequency and auditory hallucination and delusions was observed in individual cases versus controls. In female Asian American, allele frequency for FMO3 257 was significantly associated with diagnosis and in males, genotype frequency for FMO3 257 and diagnosis was significantly associated.

Keywords: Olanzapine, flavin-containing monooxygenase-3, pharmacogenetics, schizophrenia, side effects, delusions, hallucinations, ethnic groups