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S014-2

Associations of Metabolic-Related Genetic Variants and Metabolic Traits in
Antipsychotic-Treated Patients with Schizophrenia

Chun-Hsin Chen

Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taiwan

Background/Objective: Genetic factors may contribute to the liability to having metabolic
abnormalities in antipsychotic-treated patients with schizophrenia. Genome-wide association studies
have shown that metabolic-related genetic variants associated with obesity or diabetes mellitus. We
investigated the association between metabolic-related genetic variants and metabolic profiles in
antipsychotic-treated patients with schizophrenia.

Method: We recruited 20-65 year-old patients with schizophrenia or schizoaffective disorder,
measured their metabolic profiles, and genotyped their metabolic-related genes, such as PPAR-γ,
leptin (LEP), INSIG2, MC4R, and FTO. Metabolic profiles included body mass index (BMI), waist
circumference (WC), blood pressure (BP), fasting plasma glucose (FPG), insulin, triglyceride,
high-density lipoprotein cholesterol (HDL-C), and Homeostasis Model of Assessment - Insulin
Resistance index [HOMA-IR]. Genetic association analyses were conducted.

Result: For PPAR-γ2, Pro12Ala, and C161T had no significant effect on obesity or metabolic traits
in antipsychotic-treated patients with schizophrenia. Haplotype analyses showed that PPARγ2 gene
polymorphisms were significantly associated with HDL-C level in men and BP in women. INSIG2
was significantly associated with FPG, MC4R was associated with WC, and LEP was associated
with BMI and WC. We found significant genotype-antipsychotic interactions of the FTO variants
with BP, lipid profiles, FPG, and HOMA-IR. In further stratified analysis, FTO variants were
significantly associated with certain metabolic traits in the clozapine/olanzapine group, whereas none
of the FTO variants were associated with metabolic parameters in the non-clozapine/olanzapine
group.

Conclusion: In these cross-sectional investigations, we found that metabolic-related genetic variants
were associated with metabolic traits in antipsychotic-treated patients with schizophrenia. The
associations and interactions of genotype, antipsychotic, and metabolic traits should be verified using
prospective design in the future.