Progranulin gene variability influences the risk for bipolar I disorder, but not bipolar II disorder

Authors

  • Daniela Galimberti,

    Corresponding author
    1. Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    • Corresponding author:

      Dr. Daniela Galimberti

      Neurology Unit

      Department of Pathophysiology and Transplantation

      University of Milan

      Fondazione Cà Granda

      IRCCS Ospedale Policlinico

      Milan 20122

      Italy

      Fax: +39-2-50320430

      E-mail: daniela.galimberti@unimi.it

    Search for more papers by this author
  • Cecilia Prunas,

    1. Psychiatry Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • Riccardo A Paoli,

    1. Psychiatry Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • Bernardo Dell'Osso,

    1. Psychiatry Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • Chiara Fenoglio,

    1. Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • Chiara Villa,

    1. Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • Carlotta Palazzo,

    1. Psychiatry Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • Michela Cigliobianco,

    1. Psychiatry Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • Giulia Camuri,

    1. Psychiatry Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • Maria Serpente,

    1. Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • Elio Scarpini,

    1. Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author
  • A Carlo Altamura

    1. Psychiatry Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
    Search for more papers by this author

Abstract

Objective

Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder.

Methods

In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels.

Results

The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33–0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p < 0.001].

Conclusions

Regarding the influence of GRN variability on BD susceptibility, the predisposing genetic background differs between BD-I and BD-II, possibly implying that pathogenic mechanisms differ between the two subtypes of BD.

Ancillary