Cover Journal of the American Veterinary Medical Association
Journal of the American Veterinary Medical Association
ISSN:
0003-1488
Publication Date:
27 Apr 2022
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Editorial Type:
Scientific Reports

ATP7A, ATP7B, and RETN genotypes in Labrador Retrievers with and without copper-associated hepatopathy

Daniel K. LangloisDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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Brendan S. M. NaglerDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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Rebecca C. SmedleyVeterinary Diagnostic Laboratory, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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Ya-Ting YangDepartment of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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Vilma Yuzbasiyan-GurkanDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI
Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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DOI:
https://doi.org/10.2460/javma.21.12.0541
Volume/Issue:
Volume 260: Issue 14
Online Publication Date:
27 Apr 2022
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Abstract

OBJECTIVE

To determine the frequency of previously reported coding variants in the ATP7A, ATP7B, and RETN genes in a US population of Labrador Retrievers and to explore potential associations of these genotypes with pathologic hepatic copper accumulation.

SAMPLE

Archived hepatic specimens from 90 Labrador Retrievers collected between 2013 and 2021.

PROCEDURES

The Michigan State University Veterinary Diagnostic Laboratory database was searched to identify archived tissues from Labrador Retrievers that had undergone hepatic histopathologic assessment. Cases were classified into control, copper-associated hepatopathy (CAH), and intermediate populations on the basis of histopathologic features and hepatic copper accumulation. The DNA was extracted from archived tissues and genotyped for reported variants in the 3 genes. Allele frequencies were determined, and associations of genotypes with CAH status were evaluated.

RESULTS

29 control dogs, 45 CAH dogs, and 16 intermediate dogs were included in the study. The overall ATP7A and RETN variant allele frequencies were 30% and 13%, respectively, and were not significantly different among control, CAH, and intermediate populations. The ATP7B variant allele frequency was significantly higher in the CAH population (30%) as compared to the control population (13%). However, 21 of 45 (47%) CAH dogs did not have an ATP7B variant allele whereas 7 of 28 (25%) control dogs did have an ATP7B variant allele.

CLINICAL RELEVANCE

Study results supported a contributory role for the ATP7B variant in CAH pathogenesis in Labrador Retrievers. However, the application of genetic testing in a clinical setting is complicated by genotypic variability within healthy and diseased dogs.

Abstract

OBJECTIVE

To determine the frequency of previously reported coding variants in the ATP7A, ATP7B, and RETN genes in a US population of Labrador Retrievers and to explore potential associations of these genotypes with pathologic hepatic copper accumulation.

SAMPLE

Archived hepatic specimens from 90 Labrador Retrievers collected between 2013 and 2021.

PROCEDURES

The Michigan State University Veterinary Diagnostic Laboratory database was searched to identify archived tissues from Labrador Retrievers that had undergone hepatic histopathologic assessment. Cases were classified into control, copper-associated hepatopathy (CAH), and intermediate populations on the basis of histopathologic features and hepatic copper accumulation. The DNA was extracted from archived tissues and genotyped for reported variants in the 3 genes. Allele frequencies were determined, and associations of genotypes with CAH status were evaluated.

RESULTS

29 control dogs, 45 CAH dogs, and 16 intermediate dogs were included in the study. The overall ATP7A and RETN variant allele frequencies were 30% and 13%, respectively, and were not significantly different among control, CAH, and intermediate populations. The ATP7B variant allele frequency was significantly higher in the CAH population (30%) as compared to the control population (13%). However, 21 of 45 (47%) CAH dogs did not have an ATP7B variant allele whereas 7 of 28 (25%) control dogs did have an ATP7B variant allele.

CLINICAL RELEVANCE

Study results supported a contributory role for the ATP7B variant in CAH pathogenesis in Labrador Retrievers. However, the application of genetic testing in a clinical setting is complicated by genotypic variability within healthy and diseased dogs.

Supplementary Materials

    • Supplementary Appendix S1 (PDF 148 KB)

Contributor Notes

Corresponding author: Dr. Langlois (langlo21@msu.edu) or Dr. Yuzbasiyan-Gurkan (vygsu@msu.edu)

Dr. Langlois and Mr. Nagler were both first authors for this study.