title: A case-control association study of the PDLIM5 gene and bipolar disorder in a Sardinian sample.
abstract: OBJECTIVE
  PDLIM5 (ENH, LIM protein) [Postsynaptic Density-95/discs large/Zone occludens-1 (PDZ) and Lin-11, Isl-1, Mec-3 (LIM) domain 5;] is an adaptor protein that selectively binds protein kinase C-epsilon (PKC epsilon) to N-type Ca channels in brain neurons. As it has been suggested that alterations in protein kinase C activity might be involved in the pathophysiology of bipolar disorder (BD), PDLIM5 might play an important role in modulating susceptibility to the disease. Earlier investigations have reported altered expression of the PDLIM5 gene in postmortem brains and leukocytes of patients with BD. In a recent study, positive association for PDLIM5 single nucleotide polymorphisms (SNPs) was shown in a Japanese bipolar sample. The aim of our study was to investigate the association between PDLIM5 SNPs and BD in a case-control sample.
  
  
  METHODS
  We genotyped SNPs rs10008257 (SNP1), rs2433320 (SNP2) and rs2433322 (SNP3) located within the 5' region of the gene in a sample that comprises of 300 bipolar patients and 300 healthy controls of Sardinian ancestry.
  
  
  RESULTS
  In single-marker analysis, no association was found for any of the SNPs tested. After correction for multiple testing, haplotype analysis showed slight statistically significant association for a rare haplotype of SNPs 1 and 2. Although the findings presented in this paper do not provide strong evidence that the PDLIM5 gene significantly affects the pathophysiology of BD, they suggest that rare variants within the promoter region of the gene may have a marginal effect on the disorder. Further investigation on independent samples and different populations is warranted.
authors.affiliation: Section of Clinical Pharmacology, Department of Neurosciences B.B. Brodie, University of Cagliari, Cagliari, Italy. cortgen@yahoo.it
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
authors.forename: Mirko
authors.initials: M
authors.lastname: Manchia
authors.forename: Francesca
authors.initials: F
authors.lastname: Manconi
authors.forename: Mariapaola
authors.initials: M
authors.lastname: Piccardi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ardau
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Severino
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007558:Italy; D060588:LIM Domain Proteins; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C512485:PDLIM5 protein, human