A single nucleotide polymorphism in glycogen synthase kinase 3-β promoter gene influences onset of illness in patients affected by bipolar disorder

Francesco Benedetti, Alessandro Bernasconi, Cristina Lorenzi, Adriana Pontiggia, Alessandro Serretti, Cristina Colombo, Enrico Smeraldi

Research output: Contribution to journalArticlepeer-review

Abstract

Genetic studies in medicine exploited age of onset as a criterion to delineate subgroups of illness. Bipolar patients stratified with this criterion were shown to share clinical characteristics and patterns of inheritance of illness. The molecular mechanisms driving the biological clock in the suprachiasmatic nucleus of the hypothalamus may play a role in mood disorders. A single nucleotide polymorphism (SNP) (-50 T/C) falling into the effective promoter region (nt -171 to +29) of the gene coding for glycogen synthase kinase 3-β (GSK3-β) has been identified. GSK3-β codes for an enzyme which is a target for the action of lithium and which is also known to regulate circadian rhythms in Drosophila. We studied the effect of this polymorphism on the age at onset of bipolar disorder type I. A homogeneous sample of 185 Italian patients affected by bipolar disorder was genotyped. Age at onset was retrospectively ascertained with best estimation procedures. No association was detected between GSK3-β -50 T/C SNP and the presence of bipolar illness. Homozygotes for the wild variant (T/T) showed an earlier age at onset than carriers of the mutant allele (F=5.53, d.f.=2,182, P=0.0047). Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, but caution ought to be taken in interpreting these preliminary results and future replication studies must be awaited.

Original languageEnglish
Pages (from-to)37-40
Number of pages4
JournalNeuroscience Letters
Volume355
Issue number1-2
DOIs
Publication statusPublished - Jan 23 2004

Keywords

  • Age at onset
  • Bipolar disorder
  • Endophenotype
  • Glycogen synthase kinase 3-β
  • SHAGGY

ASJC Scopus subject areas

  • Neuroscience(all)

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