Metabolic syndrome in patients taking clozapine: prevalence and influence of catechol-O-methyltransferase genotype
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.
This study aimed at determining the prevalence and influence of COMT on MetS among a population undergoing long-term clozapine treatment.
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.
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).
Our findings suggest a potential association between rs4680 in COMT and elevated TG levels, particularly among female patients.
KeywordClozapine COMT Metabolic syndrome Triglyceride Association
This work was supported by the National Natural Science Foundation of China (81000581), the Shanghai Science & Technology Development Foundation (12140904200), the China Postdoctoral Science Foundation (2013M530410), and the National Key Clinical Disciplines at Shanghai Mental Health Center (OMA-MH, 2011-873).
Conflict of interest
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