Cashman John R, Zhang Jun, Nelson Matthew R, Braun Andreas
Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
Drug Metab Lett. 2008 Apr;2(2):100-14. doi: 10.2174/187231208784040942.
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.
对接受奥氮平治疗的欧洲裔、拉丁裔、非裔和亚裔美国精神分裂症患者的含黄素单加氧酶3(FMO3)基因型数据与年龄、性别和种族/族裔匹配的对照组进行了比较。研究了与病例对照状态相关的单核苷酸多态性和单倍型,以确定FMO3在奥氮平治疗反应中的潜在作用。还研究了副作用与FMO3基因型和等位基因频率之间的关系。对于欧洲裔美国人,在FMO3 158和257等位基因及基因型频率与精神分裂症的妄想、幻觉以及体重增加/食欲增加之间,观察到个体病例与对照组存在显著差异,但在重复人群中未观察到这种情况。对于拉丁裔美国人,在FMO3 158和257与精神分裂症的妄想以及幻觉和妄想方面,观察到个体病例与对照组存在显著差异。嗜睡和体重增加与308等位基因相关。对于非裔美国人,等位基因频率与诊断的比较显示,个体病例与对照组对158等位基因存在显著依赖性。FMO3基因型和等位基因频率与幻听或妄想无显著关联。对于亚裔美国人,在个体病例与对照组中,等位基因或基因型频率与幻听和妄想未观察到显著差异。在亚裔美国女性中,FMO3 257的等位基因频率与诊断显著相关,在男性中,FMO3 257的基因型频率与诊断显著相关。