title: The p. R151C Polymorphism in MC1R Gene Modifies the Age of Onset in Spanish Huntington's Disease Patients.
abstract: The expansion of CAG repeats (≥36 CAG) in the HTT gene is the only known genetic cause of Huntington's disease (HD) and the main determinant of the course of the disease. The length of the expanded CAG repeats correlates inversely with the age of onset (AOO) but does not completely determine it. We investigated the role of the melanocortin 1 receptor (MC1R) gene as a modifier factor of AOO in 600 HD patients from Spain. We sequenced the entire region of the MC1R gene and analyzed all the nonsynonymous MC1R genetic variants with a minor allele frequency of at least 0.01 in HD patients. The variability in AOO attributable to the CAG repeats and MC1R polymorphisms was evaluated using a multiple linear regression model. We found that the loss-of-function p. R151C MC1R polymorphism has a significant influence on the AOO (P = 0.004; Bonferroni-corrected P = 0.032) which explains 1.42% of the variance in AOO that cannot be accounted for by the expanded CAG repeat. Our results suggest that the MC1R gene could modify the AOO in Spanish HD patients and encourage the evaluation of loss-of-function MC1R polymorphisms in other HD populations with a higher frequency of these MC1R polymorphisms.
authors.affiliation: Dermatology Department, Melanoma Unit, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.|Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Tell-Marti
authors.affiliation: Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.|Biochemical and Molecular Genetics Service, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), 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.|Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Pol
authors.initials: P
authors.lastname: Gimenez-Xavier
authors.affiliation: Dermatology Department, Melanoma Unit, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Segu-Roig
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: Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.|Biochemical and Molecular Genetics Service, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Badenas
authors.affiliation: Laboratorio de Genética. AGC Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.affiliation: Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.|Instituto de Investigación Sanitaria Hospital La Fe, IIS-La Fe, Valencia, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Millán
authors.affiliation: Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.|Department of Genetics, Health Research Institute-Jimenez Diaz Foundation University Hospital (IIS-FJD), Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Trujillo-Tiebas
authors.affiliation: Medical Genetics Department, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, Irunlarrea 4, 31008, Pamplona, Navarra, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Ramos-Arroyo
authors.affiliation: Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.|Biochemical and Molecular Genetics Service, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Milà
authors.affiliation: Dermatology Department, Melanoma Unit, Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain. susipuig@gmail.com.|Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain. susipuig@gmail.com.|Medicine Department, Universitat de Barcelona, Barcelona, Spain. susipuig@gmail.com.
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
mesh_terms: D017668:Age of Onset; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*
chemical_list: D044102:Receptor, Melanocortin, Type 1
keywords: Age of onset; Huntington’s disease; Melanocortin 1 receptor (MC1R) gene; Neurodegenerative diseases; p. R151C