title: A Common Variant in the MC1R Gene (p.V92M) is associated with Alzheimer's Disease Risk.
abstract: Despite the recent identification of some novel risk genes for Alzheimer's disease (AD), the genetic etiology of late-onset Alzheimer's disease (LOAD) remains largely unknown. The inclusion of these novel risk genes to the risk attributable to the APOE gene accounts for roughly half of the total genetic variance in LOAD. The evidence indicates that undiscovered genetic factors may contribute to AD susceptibility. In the present study, we sequenced the MC1R gene in 525 Spanish LOAD patients and in 160 controls. We observed that a common MC1R variant p.V92M (rs2228479), not related to pigmentation traits, was present in 72 (14%) patients and 15 (9%) controls and confers increased risk of developing LOAD (OR: 1.99, 95% CI: 1.08-3.64, p = 0.026), especially in those patients whose genetic risk could not be explained by APOE genotype. This association remains and even increased in the subset of 69 patients with typical AD cerebrospinal fluid profile (OR: 3.40 95% CI: 1.40-8.27, p = 0.007). We did not find an association between p.V92M and age of onset of AD. Further studies are necessary to elucidate the role of MC1R in brain cells through the different MC1R pathways.
authors.affiliation: Dermatology Department, Melanoma Unit, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.|Centro Investigaciòn Biomèdica en Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Tell-Marti
authors.affiliation: Biochemical and Molecular Genetics Service, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.|Centro Investigaciòn Biomèdica en Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain.
authors.forename: Joan Anton
authors.initials: JA
authors.lastname: Puig-Butille
authors.affiliation: Dermatology Department, Melanoma Unit, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Potrony
authors.affiliation: RTI Healtlh Solutions, Travesera de Gracia 56 Atic 1era, Barcelona, Spain.
authors.forename: Estel
authors.initials: E
authors.lastname: Plana
authors.affiliation: Biochemical and Molecular Genetics Service, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.|Centro Investigaciòn Biomèdica en Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Badenas
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Antonell
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Sanchez-Valle
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Molinuevo
authors.affiliation: Memory Unit, Neurology Department, Hospital de Sant Pau (Sant Pau Biomedical Research Institute), Universitat Autònoma de Barcelona, Barcelona, Spain.|CIBERNED, Center of Networker Biomedical Research into Neurodegenerative Diseases, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
authors.affiliation: Memory Unit, Neurology Department, Hospital de Sant Pau (Sant Pau Biomedical Research Institute), Universitat Autònoma de Barcelona, Barcelona, Spain.|CIBERNED, Center of Networker Biomedical Research into Neurodegenerative Diseases, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alcolea
authors.affiliation: Memory Unit, Neurology Department, Hospital de Sant Pau (Sant Pau Biomedical Research Institute), Universitat Autònoma de Barcelona, Barcelona, Spain.|CIBERNED, Center of Networker Biomedical Research into Neurodegenerative Diseases, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.affiliation: Laboratory of Neurodegenerative Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Hospital Clínic de Barcelona-Centro de Investigaciòn sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, Barcelona, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Fernández-Santiago
authors.affiliation: Memory Unit, Neurology Department, Hospital de Sant Pau (Sant Pau Biomedical Research Institute), Universitat Autònoma de Barcelona, Barcelona, Spain.|CIBERNED, Center of Networker Biomedical Research into Neurodegenerative Diseases, Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Lladó
authors.affiliation: Dermatology Department, Melanoma Unit, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.|Centro Investigaciòn Biomèdica en Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain.|Medicine Department, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D044102:Receptor, Melanocortin, Type 1
keywords: Cerebrospinal fluid biomarkers; common variant; late-onset Alzheimer’s disease; melanocortin 1 receptor (MC1R) gene; p.V92M; risk