Metabolic syndrome in patients taking clozapine: prevalence and influence of catechol-O-methyltransferase genotype.
BACKGROUND
Metabolic syndrome (MetS) has consistently been identified as an adverse effect of long-term treatment with atypical antipsychotics (AAPs) such as clozapine. Elevated serum homocysteine concentration has been found to act as an independent risk factor for MetS, and catechol-O-methyltransferase (COMT) catalyzes the homocysteine metabolism. We accordingly hypothesized that COMT dysregulation may confer the susceptibility to MetS induced by AAPs, potentially in a gender-specific manner, because the interaction effects of COMT and gender have been consistently reported.


OBJECTIVE
This study aimed at determining the prevalence and influence of COMT on MetS among a population undergoing long-term clozapine treatment.


METHODS
A total of 468 schizophrenia patients taking clozapine were divided into two groups, those experiencing MetS and non-MetS. We genotyped three functional variants (rs4633, rs4680, and rs4818) in COMT and measured the serum levels of fasting homocysteine, glucose, triglyceride (TG), and high-density lipoprotein cholesterol.


RESULTS
MetS was found in 202/468 (43.2 %) of all the patients, with 40.2 % prevalence (138/343) in males and 51.2 % (64/125) in females. Patients with MetS had notably higher metabolic parameters than those without MetS. The mean levels of homocysteine in patients with MetS were significantly higher than those without MetS. We found a positive association between the rs4680 polymorphism and the serum triglyceride levels (corrected P = 0.024). Further analysis revealed that the rs4680 Met allele was significantly associated with increased triglyceride levels among female patients (P = 0.009), but not among males (P = 0.07).


CONCLUSIONS
Our findings suggest a potential association between rs4680 in COMT and elevated TG levels, particularly among female patients.
Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai, 200030, China.
Yi
Y
Zhang
Meijuan
M
Chen
Jun
J
Chen
Zhiguo
Z
Wu
Shunying
S
Yu
Yiru
Y
Fang
Chen
C
Zhang
D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001786:Blood Glucose; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D014150:Antipsychotic Agents; D001786:Blood Glucose; D008076:Cholesterol, HDL; D014280:Triglycerides; D002394:Catechol O-Methyltransferase; D003024:Clozapine