P.3.c.001 Association between HTR2C polymorphisms and the metabolic syndrome in patients using antipsychotics: a replication study

Abstract

Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association between the variant rs1414334 C-allele and an increased prevalence of the metabolic syndrome. The objective of the current study was to try to replicate our previous findings in a different patient sample. Methods: Patients were included from an ongoing 'Pharmacotherapy Monitoring and Outcome survey': PHAMOUS (http:// www.phamous.eu/). PHAMOUS combines a yearly somatic screening with routine outcome assessment in patients using antipsychotics. A cross-sectional design was used to investigate the association between HTR2C variants and the metabolic syndrome in patients diagnosed with schizophrenia or related disorders. Patients, ≥18 years, were eligible for inclusion if they used antipsychotic drugs and gave informed consent. Primary endpoint was prevalence of the metabolic syndrome, as defined by the definition by the National Cholesterol Education Program's Adult Treatment panel III (NCEP:ATP IIIa). HbA1c was used when fasting glucose values were unavailable. Secondary endpoints were associations between HTR2c polymorphisms and individual parameters contributing to the metabolic syndrome, as well as effects of individual antipsychotics. Primary determinants were the 759 C/T and rs1414334:C>G polymorphisms in the X-linked HTR2c gene. The association between HTR2C genotypes (carriership of the variant HTR2C allele) and prevalence of the metabolic syndrome was investigated with logistic regression. Results were expressed as Odds Ratio's with a 95% confidence interval (95% CI). Data were investigated for potential confounding effects of age, ethnicity, DSM-IV diagnosis, gender, use of SSRI's and antipsychotic drugs. Results: In total, 186 patients, mainly male (68%) and Caucasian (93%) were included. Olanzapine (23%), risperidone (22%) and clozapine (17%) where the most frequently prescribed antipsychotic drugs. The variant rs1414334 C-allele was significantly associated with the metabolic syndrome (OR 3.99; 95% CI 1.40-11.33) (table 1). There was a trend for an association between the variant rs1414334 C-allele and the metabolic syndrome in patients using risperidone (OR 16.50; 95% CI 0.73-375.43, p 0.08). There was also a trend for an association between the variant rs1414334 C-allele and an increased risk for reaching the cutoff points for lowered HDL (OR 2.47; 95% CI 0.95-6.42) and elevated triglyceride levels (OR 2.21; 95% CI 0. 94-5.18) respectively).(Table presented) Conclusions: This study confirms our previous findings that the variant C-allele of the rs1414334 polymorphism is associated with the metabolic syndrome.