Is the Gly82Ser polymorphism in the RAGE gene relevant to schizophrenia and the personality trait psychoticism?

Is the Gly82Ser polymorphism in the RAGE gene relevant to schizophrenia and the personality trait psychoticism?

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J Psychiatry Neurosci 2012;37(2):113-21

Petra Suchankova, PhD; Jonas Klang, MD; Carin Cavanna, MD; Göran Holm, MD, PhD; Staffan Nilsson, PhD; Erik G. Jönsson, MD, PhD; Agneta Ekman, PhD

Suchankova, Klang, Cavanna, Ekman — Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden; Holm — Department of Metabolism and Cardiovascular Research, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Sweden; Nilsson — Departmentof Mathematical Statistics, Institute of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden; Jönsson — Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden

Abstract

Background: The receptor for advanced glycation end products (RAGE) is the main receptor for S100B, an astrogial proinflammatory mediator that has been suggested to be involved in the pathophysiology of schizophrenia. To further elucidate the possible relevance of inflammation for mental functions, we investigated a functional polymorphism in the gene coding for RAGE in relation to personality traits and susceptibility to schizophrenia.
Methods: We studied the Gly82Ser polymorphism (rs2070600, 244G>A) in 2 population-based cohorts of middle-aged participants assessed using the Karolinska Scales of Personality. In addition, we compared genotype frequencies between patients with schizophrenia and controls.
Results: The population-based cohorts included 270 women and 247 men, and the case–control study involved 138 patients with schizophrenia and 258 controls. In the population-based cohorts, 82Ser carriers were found to have significantly higher scores for the psychoticism personality trait comprising the detachment and suspicion subscales. The case–control study revealed that the 82Ser allele was significantly more frequent among patients than controls.
Limitations: This study was limited by the modest sample size and the use of a self-report measure to assess personality traits.
Conclusion: Our findings suggest that the proven relation between certain personality traits and schizophrenia can at least to some extent be explained on a genetic level. Also, the activated S100B–RAGE axis may be an underlying cause, not only a consequence, of the disease.


Submitted Mar. 8, 2011; Revised June 2, 2011; Accepted June 21, 2011.

Acknowledgments: We gratefully acknowledge Laura Fratiglioni and Lars Bäckman at the Kungsholmen project, who kindly permitted us to use their cohort as controls in the present study. We also thank Gunilla Bourghardt and Inger Oscarsson for invaluable technical assistance. This study was supported by the Foundation for Psychosomatic and Clinical Research.

Competing interests: None declared for P. Suchankova, J. Klang, C. Cavanna, G. Holm, S. Nilsson and A. Ekman. E.G. Jönsson declared having received grant support from the Swedish Research Council (K2007-62X-15078-04-3, K2008-62P-20597-01-3).

Contributors: P. Suchankova designed the study. P. Suchankova, J. Klang, C. Cavanna and E.G. Jönsson acquired the data. P. Suchankova, J. Klang, C. Cavanna, G. Holm, S. Nilsson and A. Ekman analyzed the data. P. Suchankova, S. Nilsson and A. Ekman wrote the article. All authors reviewed the article and approved its publication.

DOI: 10.1503/jpn.110024

Correspondence to: P. Suchankova, Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, PO Box 431, SE-405 30 Gothenburg, Sweden; petra.suchankova@pharm.gu.se