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Association Study of Arcuate Nucleus Neuropeptide Y Neuron Receptor Gene Variation And Serum Npy Levels in Clozapine Treated Patients With Schizophrenia

Published online by Cambridge University Press:  10 November 2016

J.-P. Klemettilä ,
O. Kampman ,
A. Solismaa ,
L.-P. Lyytikäinen ,
N. Seppälä ,
M. Viikki ,
M. Hämäläinen ,
E. Moilanen ,
N. Mononen  and
T. Lehtimäki
...Show all authors
J.-P. Klemettilä*
Affiliation:
Tampere University Hospital, Department of Psychiatry, Pitkäniemi Hospital, 33380Pitkäniemi, Finland
O. Kampman
Affiliation:
University of Tampere, School of Medicine, 33014Tampere, Finland Seinäjoki Hospital District, Department of Psychiatry, 60220Seinäjoki, Finland
A. Solismaa
Affiliation:
University of Tampere, School of Medicine, 33014Tampere, Finland Seinäjoki Hospital District, Department of Psychiatry, 60220Seinäjoki, Finland
L.-P. Lyytikäinen
Affiliation:
Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere, School of Medicine, 33014, TampereFinland
N. Seppälä
Affiliation:
Tampere University Hospital, Department of Psychiatry, Pitkäniemi Hospital, 33380Pitkäniemi, Finland
M. Viikki
Affiliation:
University of Tampere, School of Medicine, 33014Tampere, Finland Tampere Mental Health Centre, Hallituskatu 8B, 33200Tampere, Finland
M. Hämäläinen
Affiliation:
The Immunopharmacology Research Group, University of Tampere, School of Medicine and Tampere University Hospital, 33014Tampere, Finland
E. Moilanen
Affiliation:
The Immunopharmacology Research Group, University of Tampere, School of Medicine and Tampere University Hospital, 33014Tampere, Finland
N. Mononen
Affiliation:
Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere, School of Medicine, 33014, TampereFinland
T. Lehtimäki
Affiliation:
Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere, School of Medicine, 33014, TampereFinland
E. Leinonen
Affiliation:
Tampere University Hospital, Department of Psychiatry, Pitkäniemi Hospital, 33380Pitkäniemi, Finland University of Tampere, School of Medicine, 33014Tampere, Finland
*
* Corresponding author. Tel.: +358 50 5928308. E-mail address:[email protected] (J.-P. Klemettilä).
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Abstract

Background

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.

Subjects and methods

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.

Results

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 GRSNPY remained non-significant (P = 0.078).

Conclusions

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.

Keywords

SchizophreniaGeneticsNPY receptorWeight gainPolymorphismResistin
Type
Original article
Information
European Psychiatry , Volume 40 , February 2017 , pp. 13 - 19
Copyright
Copyright © Elsevier Masson SAS 2017

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