Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease

Kathryn M. Meurs; Lisbeth H. Olsen; Maria J. Reimann; Bruce W. Keene; Clarke E. Atkins; Darcy Adin; Brent Aona; Julia Condit; Teresa Defrancesco; Yamir Reina-Doreste; Joshua A. Stern; Sandra Tou; Jessica Ward; Kathleen Woodruff

doi:10.1097/FPC.0000000000000322

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease

Kathryn M. Meurs^*, Lisbeth H. Olsen, Maria J. Reimann, Bruce W. Keene, Clarke E. Atkins, Darcy Adin, Brent Aona, Julia Condit, Teresa Defrancesco, Yamir Reina-Doreste, Joshua A. Stern, Sandra Tou, Jessica Ward, Kathleen Woodruff

^*Corresponding author for this work

Lifepharm

6 Citations (Scopus)

Abstract

Objectives Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Methods Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Results Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). Conclusion The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

Original language	English
Journal	Pharmacogenetics and Genomics
Volume	28
Issue number	2
Pages (from-to)	37-40
Number of pages	4
ISSN	1744-6872
DOIs	https://doi.org/10.1097/FPC.0000000000000322
Publication status	Published - 2018

Keywords

angiotensin-converting enzyme
angiotensin-converting enzyme inhibitor
dog
polymorphism
valve

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Meurs, K. M., Olsen, L. H., Reimann, M. J., Keene, B. W., Atkins, C. E., Adin, D., Aona, B., Condit, J., Defrancesco, T., Reina-Doreste, Y., Stern, J. A., Tou, S., Ward, J., & Woodruff, K. (2018). Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease. Pharmacogenetics and Genomics, 28(2), 37-40. https://doi.org/10.1097/FPC.0000000000000322

Meurs, KM, Olsen, LH, Reimann, MJ, Keene, BW, Atkins, CE, Adin, D, Aona, B, Condit, J, Defrancesco, T, Reina-Doreste, Y, Stern, JA, Tou, S, Ward, J & Woodruff, K 2018, 'Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease', Pharmacogenetics and Genomics, vol. 28, no. 2, pp. 37-40. https://doi.org/10.1097/FPC.0000000000000322

@article{48bfc5f832dd46bd90684fd5351b030b,

title = "Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease",

abstract = "Objectives Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Methods Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Results Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). Conclusion The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.",

keywords = "angiotensin-converting enzyme, angiotensin-converting enzyme inhibitor, dog, polymorphism, valve",

author = "Meurs, {Kathryn M.} and Olsen, {Lisbeth H.} and Reimann, {Maria J.} and Keene, {Bruce W.} and Atkins, {Clarke E.} and Darcy Adin and Brent Aona and Julia Condit and Teresa Defrancesco and Yamir Reina-Doreste and Stern, {Joshua A.} and Sandra Tou and Jessica Ward and Kathleen Woodruff",

year = "2018",

doi = "10.1097/FPC.0000000000000322",

language = "English",

volume = "28",

pages = "37--40",

journal = "Pharmacogenetics and Genomics",

issn = "1744-6872",

publisher = "Lippincott Williams & Wilkins",

number = "2",

}

TY - JOUR

T1 - Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease

AU - Meurs, Kathryn M.

AU - Olsen, Lisbeth H.

AU - Reimann, Maria J.

AU - Keene, Bruce W.

AU - Atkins, Clarke E.

AU - Adin, Darcy

AU - Aona, Brent

AU - Condit, Julia

AU - Defrancesco, Teresa

AU - Reina-Doreste, Yamir

AU - Stern, Joshua A.

AU - Tou, Sandra

AU - Ward, Jessica

AU - Woodruff, Kathleen

PY - 2018

Y1 - 2018

N2 - Objectives Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Methods Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Results Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). Conclusion The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

AB - Objectives Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Methods Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Results Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). Conclusion The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

KW - angiotensin-converting enzyme

KW - angiotensin-converting enzyme inhibitor

KW - dog

KW - polymorphism

KW - valve

U2 - 10.1097/FPC.0000000000000322

DO - 10.1097/FPC.0000000000000322

M3 - Journal article

C2 - 29200408

AN - SCOPUS:85043600316

SN - 1744-6872

VL - 28

SP - 37

EP - 40

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

IS - 2

ER -

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease

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Keywords

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