Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific member of the protein tyrosine phosphatase (PTP) family that has been implicated in learning and memory. In this study, we examined the association of the protein tyrosine phosphatase non-receptor 5 (PTPN5) gene, which encodes for STEP, with both schizophrenia and cognitive functioning in the Israeli Jewish population.
A schizophrenia (SZ) case–control study of 868 participants was carried out (286 patients and 582 controls). Eleven PTPN5 tagging single-nucleotide polymorphisms (SNPs) were selected and single markers and haplotype association analyses were carried out. A cognitive variability study included 437 healthy women who completed a computerized cognitive battery. We performed univariate associations between the SNPs and cognitive performance. The possible functional role of these variants was examined by studying their association with gene expression levels in the brain.
In the SZ study, we found a nominal association in the whole sample between rs4075664 and SZ. Male patients with SZ showed a more significant association for three SNPs (rs4075664, rs2278732, and rs4757710). Haplotypes of the studied SNPs were associated with SZ both in the overall sample and within the male subsample. Expression analysis provided some support for the effects of the associated SNPs on PTPN5 expression level. The cognitive variability study showed positive associations between PTPN5 SNPs and different cognitive subtests. Principal component analysis showed an ‘attention index’ neurocognitive component that was associated with two SNP pairs (rs10832983×rs10766504 and rs7932938×rs4757718).
The results imply a model in which PTPN5 may play a role in normal cognitive functioning and contribute to aspects of the neuropathology of SZ.
aDepartment of Psychiatry, Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center
bJerusalem Mental Health Center, Jerusalem, Israel
cChild Study Center, Yale University School of Medicine, New Haven, Connecticut, USA
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.psychgenetics.com).This study was conducted as part of the requirements for Ilana Pelov’s MD degree at the Hadassah-Hebrew University School of Medicine.
Ilana Pelov and Omri Teltsh contributed equally to the writing of this article.
Correspondence to Dr Yoav Kohn, MD, Department of Psychiatry, Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem 91120, Israel Tel: +972 2 570 5128; fax: +972 2 534 0024; e-mail: firstname.lastname@example.org
Received May 9, 2011
Accepted October 3, 2011