DNA microarray technology in the clinical environment: the AmpliChip CYP450 test for CYP2D6 and CYP2C19 genotyping.

INTRODUCTION: An important technological advance in genetic testing is the DNA microarray, which allows for the simultaneous testing of thousands of DNA sequences. The AmpliChip CYP450 Test employs this microarray technology for cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these genes are responsible for the metabolism of many widely prescribed drugs. The objectives of this study were to identify CYP2D6 and CYP2C19 alleles and phenotypes in a psychiatric patient population in Kentucky, and to describe practical issues associated with DNA microarray technology. METHODS: A total of 4,532 psychiatric patients were recruited from three state hospitals in Kentucky. Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip CYP450 Test to derive a predicted phenotype. RESULTS: In this cohort, the overall prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the Caucasians (95% CI 7.4%, 9.%) and 1.8% in the African Americans (95% CI 0.9%, 3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI 1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%) and 4.0% in African Americans (95% CI 2.6%, 6.1%). CONCLUSION: We also propose a numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid clinicians in determining treatment strategy for patients receiving therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene products.

A clinical study of the association of antipsychotics with hyperlipidemia.

Following a prior Kentucky clinical practice study on metabolic syndrome, serum glucose and lipid levels were used in a new sample to determine whether after correcting for confounding factors, olanzapine hyperlipidemia risk may be higher under naturalistic non-randomized treatment. Serum glucose, total cholesterol, HDL cholesterol and triglyceride levels were assessed in 360 patients with severe mental illnesses. The initial goal was to focus on olanzapine lipid profiles, but visual data inspection indicated that quetiapine needed attention as well. Patients were divided into 3 groups: 57 (16%) on olanzapine, 105 (29%) on quetiapine, and 198 (55%) on other antipsychotics (risperidone, ziprasidone, aripiprazole or typicals). HDL and glucose levels were not significantly different across the three antipsychotic groups. When compared with other antipsychotics, olanzapine patients had a borderline significantly higher mean total serum cholesterol level (178 vs. 192 mg/dl, p=0.06) and mean triglyceride level (172 vs. 202 mg/dl, p=0.06). These differences became significant (p=0.006 and 0.03) after correcting for confounders. Quetiapine appeared overprescribed in patients with metabolic syndrome complications. When compared with other antipsychotics, quetiapine patients had a significantly higher mean total serum cholesterol level (178 vs. 194 mg/dl, p=0.004) and mean triglyceride level (172 vs. 225 mg/dl, p<0.001). These differences were significant (p=0.02 and <0.001) after correcting for confounders. This study is consistent with emerging literature that suggests that some antipsychotics may have direct and immediate effects on lipid levels beyond obesity effects. The effect sizes of olanzapine and quetiapine on hyperlipidemia were about 0.40 in this naturalistic study.