Careful neuropsychological testing reveals a novel genetic marker, GSTO1*C, linked to the pre-stage of Alzheimer's disease.
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.
Medical University of Vienna, Center of Physiology and Pharmacology, Institute of Physiology, Vienna, Austria.
Ellen
E
Umlauf
Medical University of Vienna, Center of Physiology and Pharmacology, Institute of Physiology, Vienna, Austria.
Eduard
E
Rappold
Medical University of Vienna, Center of Physiology and Pharmacology, Institute of Physiology, Vienna, Austria.
Bettina
B
Schiller
SMZ Otto Wagner Spital, 3rd Department of Psychiatry, Vienna, Austria.
Petra
P
Fuchs
SMZ Ost, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria.
Michael
M
Rainer
Medical University of Vienna, Surgery Research Laboratory, Department of Surgery, Vienna, Austria.
Brigitte
B
Wolf
Medical University of Vienna, Center of Physiology and Pharmacology, Institute of Physiology, Vienna, Austria.
Maria
M
Zellner
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D016022:Case-Control Studies; D060825:Cognitive Dysfunction; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D000073216:Mental Status and Dementia Tests; D020125:Mutation, Missense; D009483:Neuropsychological Tests; D012044:Regression Analysis
D053327:Apolipoprotein E4; D005819:Genetic Markers; C490476:GSTO1 protein, human; D005982:Glutathione Transferase
Alzheimer’s disease; CERAD-Plus; Gerotarget; MCI; MMSE; well-defined control group