title: Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia.
abstract: Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment.
authors.affiliation: Department of Psychiatry, Pitkäniemi Hospital, Tampere University Hospital, 33380 Pitkäniemi, Finland. Electronic address: jari-pekka.klemettila@pshp.fi.
authors.forename: J-P
authors.initials: JP
authors.lastname: Klemettilä
authors.affiliation: School of Medicine, University of Tampere, 33014 Tampere, Finland; Department of Psychiatry, Seinäjoki Hospital District, 60220 Seinäjoki, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Kampman
authors.affiliation: Department of Psychiatry, Satakunta Hospital District, 28500 Pori, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Seppälä
authors.affiliation: School of Medicine, University of Tampere, 33014 Tampere, Finland; Tampere Mental Health Centre, Hallituskatu 8B, 33200 Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Viikki
authors.affiliation: The Immunopharmacology Research Group, School of Medicine, University of Tampere and Tampere University Hospital, 33014 Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Hämäläinen
authors.affiliation: The Immunopharmacology Research Group, School of Medicine, University of Tampere and Tampere University Hospital, 33014 Tampere, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Moilanen
authors.affiliation: Fimlab Laboratories, Department of Clinical Chemistry, School of Medicine, University of Tampere, 33014 Tampere, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Mononen
authors.affiliation: Fimlab Laboratories, Department of Clinical Chemistry, School of Medicine, University of Tampere, 33014 Tampere, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Department of Psychiatry, Pitkäniemi Hospital, Tampere University Hospital, 33380 Pitkäniemi, Finland; School of Medicine, University of Tampere, 33014 Tampere, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Leinonen
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects*; D011416:Complement Factor D / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044405:Receptor, Serotonin, 5-HT2C / Q000097:blood* / Q000235:genetics*; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D014150:Antipsychotic Agents; D015415:Biomarkers; C507763:IL1RN protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D020738:Leptin; D044405:Receptor, Serotonin, 5-HT2C; D002097:C-Reactive Protein; D011416:Complement Factor D; D003024:Clozapine
keywords: Adipokine; Adipsin; Cytokine; Weight gain; rs1414334; rs1501299; rs7799039