A case–control association study of the PDLIM5 gene and... : Psychiatric Genetics (original) (raw)

ORIGINAL ARTICLES

A case–control association study of the PDLIM5 gene and bipolar disorder in a Sardinian sample

Squassina, Alessio; Manchia, Mirko; Manconi, Francesca; Piccardi, Mariapaola; Ardau, Raffaella; Chillotti, Caterina; Severino, Giovanni; Del Zompo, Maria

Section of Clinical Pharmacology, Department of Neurosciences ‘B.B. Brodie’, University of Cagliari, Cagliari, Italy

Correspondence to Dr Alessio Squassina, PhD, Laboratory of Molecular Genetics, Section of Clinical Pharmacology, Department of Neurosciences ‘B.B. Brodie’, University of Cagliari, SS 554, Monserrato, Cagliari, Italy

Tel: +39 0706 754334; fax: +39 0706 754320; e-mail: [email protected]

Received 20 July 2007 Accepted 26 September 2007

Abstract

Objectives

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-ε (PKCε) to N-type Ca2+ 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.