Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Careful neuropsychological testing reveals a novel genetic marker, GSTO1*C, linked to the pre-stage of Alzheimer’s disease

Ellen Umlauf, Eduard Rappold, Bettina Schiller, Petra Fuchs, Michael Rainer, Brigitte Wolf and Maria Zellner _

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Oncotarget. 2016; 7:39108-39117. https://doi.org/10.18632/oncotarget.9773

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Abstract

Ellen Umlauf1, Eduard Rappold1, Bettina Schiller1, Petra Fuchs2, Michael Rainer3, Brigitte Wolf4 and Maria Zellner1

1 Medical University of Vienna, Center of Physiology and Pharmacology, Institute of Physiology, Vienna, Austria

2 SMZ Otto Wagner Spital, 3rd Department of Psychiatry, Vienna, Austria

3 SMZ Ost, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria

4 Medical University of Vienna, Surgery Research Laboratory, Department of Surgery, Vienna, Austria

Correspondence to:

Maria Zellner, email:

Keywords: Alzheimer’s disease, MCI, CERAD-Plus, MMSE, well-defined control group, Gerotarget

Received: November 19, 2015 Accepted: May 25, 2016 Published: June 01, 2016

Abstract

Approximately 30 million people currently suffer from late-onset Alzheimer’s disease (LOAD) worldwide. Twin studies demonstrated that 60 to 80% of LOAD is genetically determined, 20% of which remaining unassigned. This case-control study included 118 cognitively healthy controls, 52 patients with mild cognitive impairment (MCI; the pre-stage of LOAD) and 71 LOAD patients. The participants were genotyped for the genetic LOAD marker apolipoprotein E4 (APOE4) and the single-nucleotide polymorphism rs4925 in glutathione S-transferase omega-1 (GSTO1). Additive logistic regression showed a novel, statistically significant association of the major allele GSTO1*C with MCI (OR1.9; p = 0.032). However, identification of significant SNP-disease relations required well-defined study groups. When classifying participants solely by the short Mini Mental State examination (MMSE), the associations of GSTO1*C and the reference marker APOE4 with MCI were cancelled. Moreover, even identifying only the control group by MMSE nullified a statistically significant association (OR1.8; p = 0.045) between GSTO1*C and LOAD. In contrast, these statistical relations were retained when the detailed Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-Plus) test battery was used. Hence, besides proposing rs4925 as a genetic marker for cognitive impairment, this work also emphasized the importance of carefully characterized controls in addition to well-diagnosed patients in case-control studies.


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