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

// Ellen Umlauf 1 , Eduard Rappold 1 , Bettina Schiller 1 , Petra Fuchs 2 , Michael Rainer 3 , Brigitte Wolf 4 and Maria Zellner 1 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 fur Gedachtnis- 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.