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HTR2C Gene Polymorphisms and the Metabolic Syndrome in Patients With Schizophrenia: A Replication Study

Mulder, Hans PharmD*†; Cohen, Dan MD, PhD‡§; Scheffer, Hans PharmD, PhD; Gispen-de Wied, Christine PhD¶#; Arends, Johan MD**; Wilmink, Frederik W. MD, PhD**; Franke, Barbara PhD∥††; Egberts, Antoine C.G. PhD*‡‡

Journal of Clinical Psychopharmacology: February 2009 - Volume 29 - Issue 1 - p 16-20
doi: 10.1097/JCP.0b013e3181934462
Original Contributions
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In a previous study, we found an association between 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C) polymorphisms and the occurrence of the metabolic syndrome in patients using antipsychotics. In the current study, we set out to replicate our findings in another sample of patients and to explore in a pooled analysis of both samples the influence of the effect of individual antipsychotics. Data for this cross-sectional study came from 2 different samples, the original sample (n = 112) and the replication sample (n = 164). Primary end point was the prevalence of the metabolic syndrome as classified by a modified version of the National Cholesterol Education Program's Adult Treatment Panel III. Primary determinants were polymorphisms in the promoter region of the HTR2C gene [HTR2C:c.1−142948(GT)n, rs3813929 (−759 C/T), and rs518147 (−697 G/C)] and an intragenic polymorphism (rs1414334:C>G). The variants of HTR2C:c.1−142948(GT)n (odds ratio [OR], 1.69; 95% confidence interval [CI], 0.75-3.81) and rs1414334 (OR, 2.35; 95% CI, 0.96-5.77) were not significantly associated with the metabolic syndrome in the replication sample but did show significance in the pooled analysis (OR, 2.09; 95% CI, 1.12-3.91; and OR, 2.35; 95% CI, 1.19-4.62, respectively). The variant rs1414334 C allele was specifically associated with the metabolic syndrome in patients using clozapine (OR, 9.20; 95% CI, 1.95-43.45) or risperidone (OR, 5.35; 95% CI, 1.26-22.83). This study extends previous findings to a larger sample of patients and implicates specific antipsychotic drugs. The increased risk for the metabolic syndrome is particularly strong in carriers of the rs1414334 C allele using clozapine or risperidone.

From the *Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht; †Department of Clinical Pharmacy, Wilhelmina Hospital Assen, Assen; ‡Mental Health Services GGZ-NHN, Heerhugowaard; §Clinical Epidemiology, University Medical Centre Groningen, University of Groningen, Groningen; ∥Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen; ¶Medicines Evaluation Board, The Hague; #Department of Psychiatry, University Medical Centre Utrecht, Utrecht; **Mental Health Services Drenthe, Assen; ††Department of Psychiatry, Radboud University Nijmegen Medical Centre, Nijmegen; and ‡‡Departmentof Clinical Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands.

Received May 21, 2008; accepted after revision October 23, 2008.

Reprints: Antoine C.G. Egberts, PhD, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht University, 3508 TB Utrecht, the Netherlands (e-mail: A.C.G.Egberts@pharm.uu.nl).

© 2009 Lippincott Williams & Wilkins, Inc.