CHRNA7 Gene and Response to Cholinesterase Inhibitors in an Italian Cohort of Alzheimer's Disease Patients.
Previous studies suggest that genetic variants in CHRNA7, which encodes for the major subunit of the acetylcholine receptor (α7-nAChR), are associated with the clinical response to cholinesterase inhibitors (ChEI) in Alzheimer's disease (AD) patients. We sought to replicate the association of two SNPs in the CHRNA7 gene, rs6494223 and rs8024987, with response to ChEI treatment in an Italian cohort of 169 AD patients, further extending the study to gene-level analysis. None of the tested variants was associated with clinical response. However, rs6494223 showed a consistent effect direction (OR = 1.4; p = 0.17), which after meta-analysis with previous study yielded a significant result (OR = 1.57, p = 0.02, I2 = 0%).
Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Ferdinando
F
Clarelli
Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Elisabetta
E
Mascia
Department of Neurology, San Raffaele Hospital, Milan, Italy.
Roberto
R
Santangelo
Department of Neurology, San Raffaele Hospital, Milan, Italy.
Salvatore
S
Mazzeo
Department of Neurology, San Raffaele Hospital, Milan, Italy.
Giacomo
G
Giacalone
Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cá Granda, IRCCS Ospedale Policlinico, Milan, Italy.
Daniela
D
Galimberti
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" via La Masa, Milan, Italy.
Federica
F
Fusco
Department of Neurology, Multimedica Hospital Castellanza (Va), Castellanza, Italy.
Marta
M
Zuffi
Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cá Granda, IRCCS Ospedale Policlinico, Milan, Italy.
Chiara
C
Fenoglio
Department of Neurology, Multimedica Hospital Castellanza (Va), Castellanza, Italy.
Massimo
M
Franceschi
Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cá Granda, IRCCS Ospedale Policlinico, Milan, Italy.
Elio
E
Scarpini
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" via La Masa, Milan, Italy.
Gianluigi
G
Forloni
Department of Neurology, San Raffaele Hospital, Milan, Italy.
Giuseppe
G
Magnani
Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.|Department of Neurology, San Raffaele Hospital, Milan, Italy.
Giancarlo
G
Comi
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" via La Masa, Milan, Italy.
Diego
D
Albani
Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.|Department of Neurology, San Raffaele Hospital, Milan, Italy.
Filippo
F
Martinelli Boneschi
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D018697:Nootropic Agents / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016896:Treatment Outcome; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
D002800:Cholinesterase Inhibitors; C579167:Chrna7 protein, human; D018697:Nootropic Agents; D064569:alpha7 Nicotinic Acetylcholine Receptor
Alpha7 nicotinic acetylcholine receptor; Alzheimer’s disease; biomarkers; cholinesterase inhibitors; pharmacogenetics