Impact of apolipoprotein A5 (APOA5) polymorphisms on serum triglyceride levels in schizophrenic patients under long-term atypical antipsychotic treatment

Abstract

Objectives. Schizophrenic patients treated with clozapine or olanzapine often develop hypertriglyceridemia. The apolipoprotein A5 gene (APOA5), which affects VLDL production and lipolysis, has been implicated in the triglyceride (TG) metabolism. This study examined the association of common APOA5 genetic variants and TG levels in chronically institutionalized schizophrenic patients, on a stable dose of atypical antipsychotic (clozapine, olanzapine or risperidone. Methods. The TG levels in 466 schizophrenic patients treated with clozapine (n = 182), olanzapine (n = 89) or risperidone (n = 195) were measured. Patients were genotyped for the three APOA5 single nucleotide polymorphisms (SNPs) rs662799 (–1131T > C), rs651821 (3A > G) and rs2266788 (1891T > C). Results. A gene × drug interaction with TG levels was observed. In single-marker-based analysis, the minor alleles of the two polymorphisms (–1131C and –3G) were observed to be associated with increased TGs in patients treated with risperidone, but not with clozapine or olanzapine. Haplotype analysis further revealed that carriers of the haplotype constructed with the three minor alleles had higher TG levels than those who did not carry this haplotype in patients taking risperidone (CGC^(+/+) vs. = 125.4 ± 59.1 vs. 82.2 ± 65.8, P = 0.015; CGC^{(–/+ )} vs. CGC^(–/–) = 113.7 ± 80.4 vs. 82.2 ± 65.8, P = 0.012). Conclusions. Our findings extend and add new information to the existing data regarding the association between APOA5 and TG regulation during long-term atypical antipsychotic treatment.

Key words::

• Schizophrenia
• APOA5
• single nucleotide polymorphisms
• antipsychotic
• triglyceride

Acknowledgements

The authors would like to thank National Genotyping Center of National Research Program for Genomic Medicine, National Science Council, for the support in SNP genotyping. The authors would also like to acknowledge the National Genotyping Center of National Research Program for Genomic Medicine, Taiwan (NSC98-3112-B-001-022), especially Dr Jer-Yuan Wu for his technical support. This study was supported by grant V98C1-061 from Taipei Veterans General Hospital, Taiwan, and grants NSC 95-2314-B-075-011 and NSC 97-2314-B-075-001-MY3 from National Science Council Grant, Taiwan.

Statement of Interest

The authors declare no conflict of interest.