One‑carbon metabolism factor MTHFR variant is associated with saccade latency in Spinocerebellar Ataxia type 2.

Autor: Almaguer-Mederos LE; Center for the Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín, Cuba; University of Medical Sciences of Holguín, Cuba. Electronic address: lalmaguermederos@gmail.com., Jorge-Sainz Y; University of Medical Sciences of Holguín, Cuba., Almaguer-Gotay D; Center for the Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín, Cuba; University of Medical Sciences of Holguín, Cuba., Aguilera-Rodríguez R; Center for the Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín, Cuba; University of Medical Sciences of Holguín, Cuba., Rodríguez-Labrada R; Center for the Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín, Cuba., Velázquez-Pérez L; Center for the Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín, Cuba., González-Zaldívar Y; Center for the Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín, Cuba; University of Medical Sciences of Holguín, Cuba., Cuello-Almarales D; Center for the Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín, Cuba; University of Medical Sciences of Holguín, Cuba., Vázquez-Mojena Y; Center for the Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín, Cuba., Canales-Ochoa N; Center for the Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín, Cuba., Aguiar-Santiago J; Center of Genetic Engineering and Biotechnology (CIGB), La Habana, Cuba., Auburger G; Experimental Neurology, Goethe University Medical School, Frankfurt 60590, Germany., MacLeod P; Division of Medical Genetics, Department of Pathology, Laboratory Medicine and Medical Genetics, Victoria General Hospital, Canada.
Jazyk: angličtina
Zdroj: Journal of the neurological sciences [J Neurol Sci] 2020 Feb 15; Vol. 409, pp. 116586. Date of Electronic Publication: 2019 Nov 22.
DOI: 10.1016/j.jns.2019.116586
Abstrakt: Background: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder due to a CAG-repeat expansion. This work is intended to identify modifiers of the clinical phenotype in SCA2, following up on recent genome-wide association analyses that demonstrated the prominent role of DNA-damage repair and methylation for the severity and progression of polyglutamine diseases. In particular, we assessed the impact of MTHFR as rate-limiting enzyme in DNA methylation pathways, which modulates cerebellar neurotransmission and motor neuron atrophy.
Methods: A sample of 166 Cuban SCA2 patients and of 130 healthy subjects from the same geographical and ethnic background was selected. The ATXN2 CAG repeat length was determined by PCR followed by polyacrylamide gel electrophoresis. Two amino acid substitutions known to decrease the enzyme activity of MTHFR, encoded by C677T and A1298C polymorphisms, were assessed by PCR/RFLP.
Results: No significant differences were observed for C677T or A1298C alleles or genotype frequencies between cases and controls, confirming that disease risk in SCA2 does not depend on MTHFR activity. However, MTHFR A1298C genotypes showed a significant association with saccade latency.
Conclusions: \MTHFR A1298C polymorphism is associated with saccade latency in SCA2 patients, but not with disease risk, age at onset or maximal saccade velocity. These results provide evidence that folate-mediated one‑carbon metabolism might be important in the physiopathology of SCA2.
Competing Interests: Declaration of Competing Interest The authors of the manuscript have no conflicts of interest to declare.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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