Influence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia.
BACKGROUND
Obesity and metabolic syndrome are significant problems for patients taking antipsychotic drugs. Evidence is emerging of genetic risk factors.


OBJECTIVE
To investigate the influence of two candidate genes, smoking and drug treatment on obesity and metabolic syndrome in patients with schizophrenia.


METHODS
Patients (n=134) were assessed for measures of obesity, other factors contributing to metabolic syndrome, and two genetic polymorphisms (5-HT(2C) receptor -759C/T and leptin -2548A/G).


RESULTS
Neither genotype nor smoking was significantly associated with measures of obesity. However, both leptin genotype and smoking were significantly associated with metabolic syndrome. Significant interaction occurred between the genetic polymorphisms for effects on obesity, whereby a genotype combination increased risk. Drug treatment showed significant effects on measures of obesity and triglyceride concentrations; risperidone was associated with lower values than olanzapine or clozapine.


CONCLUSIONS
The findings suggest interacting genetic risk factors and smoking influence development of metabolic syndrome in patients on antipsychotic drugs.
Division of Psychiatry and Neuroscience, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, UK.
Olga O
OO
Yevtushenko
Stephen J
SJ
Cooper
Ryan
R
O'Neill
Jennifer K
JK
Doherty
Jayne V
JV
Woodside
Gavin P
GP
Reynolds
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000209:etiology*; D009765:Obesity / Q000453:epidemiology / Q000209:etiology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D013997:Time Factors
D014150:Antipsychotic Agents; D020738:Leptin; D044405:Receptor, Serotonin, 5-HT2C