title: Association study of arcuate nucleus neuropeptide Y neuron receptor gene variation and serum NPY levels in clozapine treated patients with schizophrenia.
abstract: Antipsychotic-induced weight gain (AIWG) leads to metabolic consequences and comorbidity, social stigmatization and nonadherence in patients with schizophrenia. Neuropeptide Y (NPY) has an important role in appetite and body weight regulation. Associations between AIWG and serum NPY levels, and genetic polymorphisms (SNPs) associated with its serum levels have been little studied in these patients.
  
  
  
  Associations between serum NPY concentration and other metabolic and inflammatory markers, and 215 SNPs in 21 genes (NPY gene, NPY receptor genes and genes encoding arcuate nucleus NPY neuron receptors) were studied in 180 patients with schizophrenia on clozapine treatment.
  
  
  
  The serum levels of NPY correlated with levels of resistin (r=0.31, P<0.001) and age (r=0.22, P=0.003). In the general linear univariate model the best-fitting model with explanatory factors age, serum resistin level, serum insulin level, BMI and gender explained 18.0% (P<0.001) of the variance of serum NPY. Genetic risk score (GRSNPY) analysis found twelve significant (P<0.05) serum NPY concentration related SNPs among α7 nicotinic acetylcholine receptor gene CHRNA7, insulin receptor gene INSR, leptin receptor gene LEPR, glucocorticoid receptor (GR) gene NR3C1, and NPY gene. However, after permutation test of gene score the predictive value of GRSNPYremained non-significant (P=0.078).
  
  
  
  Serum NPY level does not seem to be a feasible biomarker of AIWG. Serum NPY level alterations are not significantly associated with the candidate gene polymorphisms studied.
authors.affiliation: Tampere University Hospital, Department of Psychiatry, Pitkäniemi Hospital, 33380 Pitkäniemi, Finland. Electronic address: jari-pekka.klemettila@pshp.fi.
authors.forename: J-P
authors.initials: JP
authors.lastname: Klemettilä
authors.affiliation: University of Tampere, School of Medicine, 33014 Tampere, Finland; Seinäjoki Hospital District, Department of Psychiatry, 60220 Seinäjoki, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Kampman
authors.affiliation: University of Tampere, School of Medicine, 33014 Tampere, Finland; Seinäjoki Hospital District, Department of Psychiatry, 60220 Seinäjoki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Solismaa
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere, School of Medicine, 33014 Tampere, Finland.
authors.forename: L-P
authors.initials: LP
authors.lastname: Lyytikäinen
authors.affiliation: Tampere University Hospital, Department of Psychiatry, Pitkäniemi Hospital, 33380 Pitkäniemi, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Seppälä
authors.affiliation: University of Tampere, School of Medicine, 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, University of Tampere, School of Medicine and Tampere University Hospital, 33014 Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Hämäläinen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere, School of Medicine and Tampere University Hospital, 33014 Tampere, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Moilanen
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere, School of Medicine, 33014 Tampere, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Mononen
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere, School of Medicine, 33014 Tampere, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Tampere University Hospital, Department of Psychiatry, Pitkäniemi Hospital, 33380 Pitkäniemi, Finland; University of Tampere, School of Medicine, 33014 Tampere, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Leinonen
mesh_terms: D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D001111:Arcuate Nucleus of Hypothalamus; D003024:Clozapine / Q000008:administration & dosage*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D010641:Phenotype; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D003024:Clozapine
keywords: Genetics; NPY receptor; Polymorphism; Resistin; Schizophrenia; Weight gain