CHRNA7 Gene and Response to Cholinesterase Inhibitors in an Italian Cohort of Alzheimer’s Disease Patients

Article type: Short Communication

Authors: Clarelli, Ferdinando^a | Mascia, Elisabetta^a | Santangelo, Roberto^b | Mazzeo, Salvatore^b | Giacalone, Giacomo^b | Galimberti, Daniela^c | Fusco, Federica^d | Zuffi, Marta^e | Fenoglio, Chiara^c | Franceschi, Massimo^e | Scarpini, Elio^c | Forloni, Gianluigi^d | Magnani, Giuseppe^b | Comi, Giancarlo^{a; b} | Albani, Diego^d | Martinelli Boneschi, Filippo^{a; b; *}

Affiliations: [a] Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy | [b] Department of Neurology, San Raffaele Hospital, Milan, Italy | [c] Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cá Granda, IRCCS Ospedale Policlinico, Milan, Italy | [d] IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri” via La Masa, Milan, Italy | [e] Department of Neurology, Multimedica Hospital Castellanza (Va), Castellanza, Italy

Correspondence: [*] Correspondence to: Filippo Martinelli Boneschi, Laboratory of Human Genetics of Neurological Disorders, CNS Inflammatory Unit, Division of Neuroscience & INSPE, San Raffaele Scientific Institute; Via Olgettina 58, 20132 Milan, Italy. Tel.: +39 02 2643 5092; Fax: +39 02 2643 5093; E-mail: martinelli.filippo@hsr.it.

Abstract: 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%).

Keywords: Alpha7 nicotinic acetylcholine receptor, Alzheimer’s disease, biomarkers, cholinesterase inhibitors, pharmacogenetics

DOI: 10.3233/JAD-160074

Journal: Journal of Alzheimer's Disease, vol. 52, no. 4, pp. 1203-1208, 2016