Genetic variation and antipsychotic drug effects on serum lipids

Evaluation of: Smith RC, Segman RH, Golcer Dubner T, Pavlov V, Lerer B: Allelic variation in ApoC3, ApoA5, and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia. Pharmacogenomics J. DOI: 10.1038/sj.tpj.6500474 (2007) (Epub ahead of print) [1] . Some newer antipsychotic drugs may raise serum lipid levels, but it is not known whether specific genetic variants affect an individual's susceptibility to this. In 189 schizophrenia patients treated with either first- or second-generation antipsychotic drugs, Smith and colleagues analyzed drug-by-genotype interaction effects on serum cholesterol and triglyceride levels using five polymorphisms in three genes that affect serum lipids: APOC3, APOA5 and LPL. Three interactions involving the APOA5 -1131 T/C polymorphism remained significant after adjustment for multiple testing; the rarer C allele was associated with higher serum cholesterol levels in patients treated with first-generation antipsychotics, and lower levels in those treated with clozapine or olanzapine. This article emphasizes aspects of their study which illustrate points that may be useful in planning future pharmacogenetic studies.