Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy.
Abstract: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is an inherited neurodegenerative disorder associated with vitamin E deficiency. In humans, polymorphisms in genes involved in vitamin E uptake and distribution determines individual vitamin E requirements. Objective: Genetic polymorphisms in genes involved in vitamin E metabolism would be associated with an increased risk of eNAD/EDM in Quarter Horses (QHs). Methods: Whole-genome sequencing: eNAD/EDM affected (n = 9, postmortem [PM]-confirmed) and control (n = 32) QHs. Results: eNAD/EDM affected (n = 39, 23-PM confirmed) and control (n = 68, 7-PM confirmed) QHs. Allele frequency (AF): Publicly available data from 504 horses across 47 breeds. Methods: Retrospective, case control study. Whole-genome sequencing was performed and genetic variants identified within 28 vitamin E candidate genes. These variants were subsequently genotyped in the validation cohort. Results: Thirty-nine confirmed variants in 15 vitamin E candidate genes were significantly associated with eNAD/EDM (P < .01). In the validation cohort, 2 intronic CD36 variants (chr4:726485 and chr4:731082) were significantly associated with eNAD/EDM in clinical (P = 2.78 × 10-4 and P = 4 × 10-4 , respectively) and PM-confirmed cases (P = 6.32 × 10-6 and 1.04 × 10-5 , respectively). Despite the significant association, variant AFs were low in the postmortem-confirmed eNAD/EDM cases (0.22-0.26). In publicly available equine genomes, AFs ranged from 0.06 to 0.1. Conclusions: Many PM-confirmed cases of eNAD/EDM were wild-type for the 2 intronic CD36 SNPs, suggesting either a false positive association or genetic heterogeneity of eNAD/EDM within the QH breed.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2023-11-08 PubMed ID: 37937700PubMed Central: PMC10800183DOI: 10.1111/jvim.16924Google Scholar: Lookup
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- Journal Article
Summary
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This research explored the genetic factors influencing the susceptibility of Quarter Horses to equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM), a neurodegenerative disease linked to vitamin E deficiency. By looking at the genetic variants in vitamin E metabolism genes, the study found two specific variants that were significantly associated with eNAD/EDM, suggesting these could be potential risk factors for the disease.
Objective and Methodology
- The study aimed to find if there was a connection between genetic polymorphisms (variations) in genes involved in vitamin E metabolism and an increased risk of eNAD/EDM in Quarter Horses.
- In order to achieve this, researchers performed Whole-genome sequencing, a process in which the complete genetic material is described, of eNAD/EDM affected and control Quarter Horses.
- They then identified genetic variants within 28 vitamin E candidate genes. These variants were subsequently genotyped in a separate validation cohort to further confirm any observations.
Results and Findings
- Of the 15 genes found to have variants, two specific variant types located in introns of the CD36 gene (non-coding sequences within a gene that are removed from the messenger RNA during processing) were significantly correlated with the presence of eNAD/EDM in clinical and post-mortem confirmed cases.
- Despite this correlation, these variant allele frequencies were low in eNAD/EDM cases confirmed after death. This infers that even though there is a link between these genetic variants and the disorder, there could be more influential factors as not all horses with the disorder had this genetic variation.
Conclusion and Implications
- The fact that many confirmed cases of eNAD/EDM had naturally occurring (wild-type) variants for the two intronic CD36 single-nucleotide polymorphisms (SNPs), indicated a possible false positive association. This highlights the possibility that eNAD/EDM in the Quarter Horse breed might be influenced by more than one set of genetic factors (genetic heterogeneity).
- This research has potential implications for the better understanding, diagnosis, and prevention of eNAD/EDM. Future research can work on clarifying the variations in genetic influences, possibly leading to more effective treatments and preventive measures.
Cite This Article
APA
Ma Y, Peng S, Donnelly CG, Ghosh S, Miller AD, Woolard K, Finno CJ.
(2023).
Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy.
J Vet Intern Med, 38(1), 417-423.
https://doi.org/10.1111/jvim.16924 Publication
Researcher Affiliations
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California 95616, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California 95616, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California 95616, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California 95616, USA.
- Department of Biomedical Sciences, Section of Anatomic Pathology, Cornell University College of Veterinary Medicine, Ithaca, New York 14853, USA.
- Department of Pathology and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, California 95616, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California 95616, USA.
MeSH Terms
- Humans
- Animals
- Horses / genetics
- Vitamin E
- Case-Control Studies
- Retrospective Studies
- Neuroaxonal Dystrophies / genetics
- Neuroaxonal Dystrophies / veterinary
- Ataxia / veterinary
- Polymorphism, Single Nucleotide
- Neurodegenerative Diseases / veterinary
- Horse Diseases / genetics
Grant Funding
- L40 TR001136 / NCATS NIH HHS
Conflict of Interest Statement
Authors declare no conflict of interest.
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