The p. R151C Polymorphism in MC1R Gene Modifies the Age of Onset in Spanish Huntington’s Disease Patients

被引：0
作者：
Gemma Tell-Marti
Joan Anton Puig-Butille
Pol Gimenez-Xavier
Ariadna Segu-Roig
Miriam Potrony
Celia Badenas
Victoria Alvarez
José M. Millán
María José Trujillo-Tiebas
María A Ramos-Arroyo
Montserrat Milà
Susana Puig
机构：
[1] Hospital Clinic & IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer),Dermatology Department, Melanoma Unit
[2] ISCIII,Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER)
[3] Hospital Clinic & IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer),Biochemical and Molecular Genetics Service
[4] Hospital Universitario Central de Asturias,Laboratorio de Genética. AGC Laboratorio de Medicina
[5] IIS-La Fe,Instituto de Investigación Sanitaria Hospital La Fe
[6] Health Research Institute–Jimenez Diaz Foundation University Hospital (IIS-FJD),Department of Genetics
[7] IdiSNA,Medical Genetics Department, Complejo Hospitalario de Navarra
[8] Navarra Institute for Health Research,Medicine Department
[9] Universitat de Barcelona,undefined
来源：
Molecular Neurobiology | 2017年 / 54卷
关键词：
Huntington’s disease; Age of onset; Melanocortin 1 receptor (; ) gene; p. R151C; Neurodegenerative diseases;
D O I：
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学科分类号：
摘要：
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.
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页码：3906 / 3910
页数：4
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