Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy.
Authors: Ma Yunzhuo, Peng Sichong, Donnelly Callum G, Ghosh Sharmila, Miller Andrew D, Woolard Kevin, Finno Carrie J
Journal: Journal of veterinary internal medicine
Summary
# Equine Neuroaxonal Dystrophy and Vitamin E Transport: Genetic Risk Factors Identified Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a progressive neurodegenerative condition linked to vitamin E deficiency, yet individual horses vary considerably in their dietary requirements for this crucial micronutrient—a pattern mirrored in human genetics, where variants in vitamin E transport genes influence susceptibility. Ma Yunzhuo and colleagues employed whole-genome sequencing in Quarter Horses to identify whether genetic polymorphisms in vitamin E metabolism pathways predispose animals to disease, initially screening nine affected and 32 control horses before validating findings in a larger cohort of 39 affected and 68 control animals. Two intronic variants in the CD36 gene (chr4:726485 and chr4:731082) emerged as significantly associated with eNAD/EDM—both in clinical cases and postmortem-confirmed diagnoses with p-values as low as 10⁻⁶—though allele frequencies remained surprisingly low (0.22–0.26 in affected horses versus 0.06–0.10 in the general population). Despite these statistically robust associations, the researchers observed that many confirmed eNAD/EDM cases were wild-type for both CD36 variants, indicating either genetic heterogeneity within the condition or the involvement of additional, as-yet-unidentified risk loci. For practitioners, these findings suggest that genetic testing for CD36 polymorphisms may eventually help identify at-risk animals, though screening cannot yet provide definitive disease prediction, and comprehensive vitamin E management strategies remain essential alongside any future genetic risk stratification.
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Practical Takeaways
- •Genetic testing for CD36 variants may help identify Quarter Horses at increased risk for eNAD/EDM, though wild-type animals can still develop disease, so vitamin E supplementation remains important for all at-risk populations
- •eNAD/EDM appears to have multiple genetic causes (heterogeneity) within Quarter Horses; breeding decisions should consider broader vitamin E metabolism pathways rather than single genes
- •Vitamin E status should be monitored and supplemented in Quarter Horses regardless of CD36 genotype, as genetic polymorphisms explain only part of disease risk
Key Findings
- •Two intronic CD36 variants (chr4:726485 and chr4:731082) were significantly associated with eNAD/EDM in Quarter Horses with p-values ranging from 2.78×10⁻⁴ to 1.04×10⁻⁵
- •Thirty-nine confirmed variants in 15 vitamin E candidate genes showed significant association with eNAD/EDM (P<0.01) in the discovery cohort
- •Despite significant statistical association, variant allele frequencies were low in postmortem-confirmed cases (0.22-0.26) compared to publicly available genomes (0.06-0.1), suggesting genetic heterogeneity
- •Many postmortem-confirmed eNAD/EDM cases were wild-type for the two CD36 SNPs, indicating either false positive association or multiple genetic causes within the breed