Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy
Abstract Background 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 require...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Journal of Veterinary Internal Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jvim.16924 |
| _version_ | 1827148306746179584 |
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| author | Yunzhuo Ma Sichong Peng Callum G. Donnelly Sharmila Ghosh Andrew D. Miller Kevin Woolard Carrie J. Finno |
| author_facet | Yunzhuo Ma Sichong Peng Callum G. Donnelly Sharmila Ghosh Andrew D. Miller Kevin Woolard Carrie J. Finno |
| author_sort | Yunzhuo Ma |
| collection | DOAJ |
| description | Abstract Background 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. Hypothesis/Objectives Genetic polymorphisms in genes involved in vitamin E metabolism would be associated with an increased risk of eNAD/EDM in Quarter Horses (QHs). Animals Whole‐genome sequencing: eNAD/EDM affected (n = 9, postmortem [PM]‐confirmed) and control (n = 32) QHs. Validation: 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 and Clinical Importance 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. |
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| format | Article |
| id | doaj.art-faaf256c03e1400c80497d644d39f5d3 |
| institution | Directory Open Access Journal |
| issn | 0891-6640 1939-1676 |
| language | English |
| last_indexed | 2025-03-20T21:00:12Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Veterinary Internal Medicine |
| spelling | doaj.art-faaf256c03e1400c80497d644d39f5d32024-08-14T04:26:12ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762024-01-0138141742310.1111/jvim.16924Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophyYunzhuo Ma0Sichong Peng1Callum G. Donnelly2Sharmila Ghosh3Andrew D. Miller4Kevin Woolard5Carrie J. Finno6Department of Population Health and Reproduction School of Veterinary Medicine, University of California‐Davis Davis, California 95616 USADepartment of Population Health and Reproduction School of Veterinary Medicine, University of California‐Davis Davis, California 95616 USADepartment of Population Health and Reproduction School of Veterinary Medicine, University of California‐Davis Davis, California 95616 USADepartment of Population Health and Reproduction School of Veterinary Medicine, University of California‐Davis Davis, California 95616 USADepartment of Biomedical Sciences, Section of Anatomic Pathology Cornell University College of Veterinary Medicine Ithaca, New York 14853 USADepartment of Pathology and Immunology School of Veterinary Medicine, University of California‐Davis Davis, California 95616 USADepartment of Population Health and Reproduction School of Veterinary Medicine, University of California‐Davis Davis, California 95616 USAAbstract Background 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. Hypothesis/Objectives Genetic polymorphisms in genes involved in vitamin E metabolism would be associated with an increased risk of eNAD/EDM in Quarter Horses (QHs). Animals Whole‐genome sequencing: eNAD/EDM affected (n = 9, postmortem [PM]‐confirmed) and control (n = 32) QHs. Validation: 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 and Clinical Importance 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.https://doi.org/10.1111/jvim.16924ataxiaequine degenerative myeloencephalopathygeneticshorse |
| spellingShingle | Yunzhuo Ma Sichong Peng Callum G. Donnelly Sharmila Ghosh Andrew D. Miller Kevin Woolard Carrie J. Finno Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy Journal of Veterinary Internal Medicine ataxia equine degenerative myeloencephalopathy genetics horse |
| title | Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy |
| title_full | Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy |
| title_fullStr | Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy |
| title_full_unstemmed | Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy |
| title_short | Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy |
| title_sort | genetic polymorphisms in vitamin e transport genes as determinants for risk of equine neuroaxonal dystrophy |
| topic | ataxia equine degenerative myeloencephalopathy genetics horse |
| url | https://doi.org/10.1111/jvim.16924 |
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