The Q7R Saitohin gene polymorphism is not associated with Alzheimer disease Sofia A. Oliveira a , Eden R. Martin a , William K. Scott a , Kristin K. Nicodemus a , Gary W. Small b , Donald E. Schmechel a , P. Murali Doraiswamy a , Allen D. Roses c , Ann M. Saunders c , John R. Gilbert a , Jonathan L. Haines d , Jeffery M. Vance a , Margaret A. Pericak-Vance a, * a Department of Medicine and Center for Human Genetics, Institute for Genome Sciences and Policy, Box 3445, Duke University Medical Center, Durham, NC 27710, USA b Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90024, USA c GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA d Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA Received 7 March 2003; received in revised form 19 May 2003; accepted 19 May 2003 Abstract Previous studies have reported conflicting results regarding the association of the Q7R polymorphism in the Saitohin gene with late-onset Alzheimer disease (AD). Given that AD is a tauopathy but no mutations or polymorphisms in Tau have been consistently associated with AD, and that Saitohin is nested in intron 9 of Tau and shares a similar expression pattern, we tested this association in 690 multiplex AD families and in a case-control sample (903 patients and 320 controls). We found no evidence of significant association of this polymorphism with risk of AD using family-based and case-control tests of association. q 2003 Published by Elsevier Science Ireland Ltd. Keywords: Parkinson disease; Saitohin; Association study; Polymorphism Apoliprotein E-4 (APOE-4) accounts for about 50% of the genetic susceptibility to late-onset Alzheimer disease (AD), suggesting the existence of additional genetic risk factors. The microtubule-associated protein Tau is the main component of the neurofibrillary tangles, a major AD neuropathological hallmark. Tau thus constitutes a good candidate gene but no mutations have been identified in AD patients and association studies have reported conflicting results [11]. Tau is mutated in frontotemporal dementia and other tauopathies, and the Tau H1 haplotype is associated with progressive supranuclear palsy and Parkinson disease. It is therefore possible that other polymorphisms in that genomic region demonstrate an association with AD. Interestingly, the Saitohin gene (STH) localizes to intron 9 of Tau and shares its expression pattern in most human tissues and brain areas [2]. Conrad et al. [2] investigated the association of the Q7R single nucleotide polymorphism (SNP) in STH with AD and found that distributions of alleles and genotypes were significantly different between 51 AD patients versus 30 controls, with the arginine (R) allele and the RR genotype significantly over-represented in AD patients (odds ratio [OR] ¼ 3.109 for allele and OR ¼ 11.92 for genotype) [2]. If this initial report was confirmed by other studies, this polymorphism would represent the second strongest genetic susceptibility factor in AD. To test these results in an additional case-control group and, for the first time, in a family-based setting, we investigated the association of this polymorphism in 690 multiplex AD families and in a case-control sample consisting of 903 patients and 320 controls. Our sample (N ¼ 690 families) for family-based associ- ation studies consists of three sets of families: the Collaborative Alzheimer Project families (ascertained through The Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (ADRC), the Department of Psychiatry and the Center for Human Genetics at Duke University, the Program in Human Genetics at Vanderbilt University, and the UCLA Neuropsychiatric Institute), families ascertained by the NIMH AD Genetics Initiative, 0304-3940/03/$ - see front matter q 2003 Published by Elsevier Science Ireland Ltd. doi:10.1016/S0304-3940(03)00670-0 Neuroscience Letters 347 (2003) 143–146 www.elsevier.com/locate/neulet * Corresponding author. Tel.: þ 1-919-684-3422; fax: þ1-919-684-2275. E-mail address: mpv@chg.duhs.duke.edu (M.A. Pericak-Vance).