Effect of Breed on Plasma Endothelin‐1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs

Höglund, Katja; Lequarré, Anne-Sophie; Ljungvall, Ingrid; Entee, Kathleen Mc; Merveille, Anne-Christine; Wiberg, Maria; Gouni, Vassiliki; Willesen, Jakob L.; Hanås, Sofia; Wess, Gerhard; Sørensen, Lars Tue; Tiret, Laurent; Kierczak, Marcin; Forsberg, Simon K. G.; Seppälä, Eija H.; Lindblad‐Toh, Kerstin; Lohi, Hannes; Chetboul, Valérie; Fredholm, Merete; Häggström, Jens

doi:10.1111/jvim.13829

Cited by 9 publications

(8 citation statements)

References 54 publications

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“…Descriptive statistics for the 40 phenotypes are listed in Supplementary Table S1. As breed differences for some phenotypes have been reported elsewhere 43,44 , breed and sex differences for these phenotypes were expected. But we have also observed differences between countries where Labrador retriever and Belgian Shepherd were sampled.…”

Section: Clinical Data Collection We Collected 40 Clinical Relevant supporting

confidence: 54%

Genome wide association study of 40 clinical measurements in eight dog breeds

Momozawa

Merveille

Battaille

et al. 2020

Sci Rep

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The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans. In this study, we investigated the genetic contribution to individual differences in 40 clinically important measurements by a genome-wide association study (GWAS) in a multinational cohort of 472 healthy dogs from eight breeds. Meta-analysis using the binary effects model after breed-specific GWAS, identified 13 genome-wide significant associations, three of them showed experimental-wide significant associations. We detected a signal at chromosome 13 for the serum concentration of alanine aminotransferase (ALT) in which we detected four breed-specific signals. A large proportion of the variance of ALT (18.1-47.7%) was explained by this locus. Similarly, a single SNP was also responsible for a large proportion of the variance (6.8-78.4%) for other measurements such as fructosamine, stress during physical exam, glucose, and morphometric measurements. The genetic contribution of single variant was much larger than in humans. These findings illustrate the importance of performing meta-analysis after breed-specific GWAS to reveal the genetic contribution to individual differences in clinically important measurements, which would lead to improvement of veterinary medicine. The domestic dogs share many diseases and phenotypes with human 1. Through two bottlenecks resulting from domestication 2 and the frequent use of specific males, each dog breed shows lower heterogeneity for disease. In humans, higher heterogeneity, meaning multiple variants with different levels of effects influencing the same disease, makes it difficult to identify genetic variants associated with disease 3. Therefore, dogs are considered an ideal model animal for identifying genes and genomic loci underlying diseases and phenotypic variation 1,4. Genome-wide association studies (GWAS) using canine single nucleotide polymorphism (SNP) chips have identified susceptibility genes and genomic loci for several complex diseases 5-10 and for many Mendelian disorders 11-16. The diagnosis of a disease often involves taking many clinical measurements including blood and urine analysis. These measurements directly reflect different aspects of the health of each individual. Individual differences in these measurements are known to be heritable in humans, and GWAS have identified genetic loci explaining these individual differences 17. A systematic analysis of 6,046 dogs has identified breed-specific differences in hematological measurements 18 , suggesting also a genetic contribution to the inter-breed variation for these

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Section: Clinical Data Collection We Collected 40 Clinical Relevant supporting

confidence: 54%

Genome wide association study of 40 clinical measurements in eight dog breeds

Momozawa

Merveille

Battaille

et al. 2020

Sci Rep

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“…Our study had some limitations. First, our study was retrospective and had a small sample size, and thus the breed, age, and sex of the dogs were not matched . Second, because some dogs with CH had received prednisolone for hepatic inflammation before sampling, the actual PAC concentrations may be higher than those that we actually measured.…”

Section: Discussionmentioning

confidence: 97%

Plasma renin activity and aldosterone concentration in dogs with acquired portosystemic collaterals

Sakamoto

Sakai

Sato

et al. 2019

Veterinary Internal Medicne

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Background: The renin-angiotensin-aldosterone system (RAAS) is activated in humans with portal hypertension (PH) associated with liver disease. However, involvement of RAAS in dogs with intrahepatic PH is not clear.Objective: To measure plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in dogs with PH (chronic hepatitis [CH] and primary hypoplasia of the portal vein [PHPV]), dogs with extrahepatic congenital portosystemic shunt (EH-CPSS), and healthy dogs and to determine whether the RAAS is activated in dogs with PH.Animals: Twenty-seven dogs with acquired portosystemic collaterals (APSCs; 15 dogs with CH, 12 dogs with PHPV), 9 dogs with EH-CPSS, and 10 healthy dogs.Methods: Retrospective study. Plasma renin activity and PAC were measured by radioimmunoassay.Results: Plasma renin activity was significantly higher in the CH group (median, 4.4 ng/mL/h) than in the EH-CPSS (median, 1.0 ng/mL/h; P < .01) and the healthy (median, 1.1 ng/mL/h; P < .01) groups. No significant differences were found between the PHPV group (median, 2.2 ng/mL/h) and other groups. Plasma aldosterone concentration was significantly higher in the CH (median, 111.0 pg/mL) and PHPV (median, 89.5 pg/mL) groups than in the EH-CPSS (median, 1.0 pg/mL; P < .001, P < .01, respectively) and healthy (median, 14.5 pg/mL; P < .001, P < .05, respectively) groups.Conclusions and Clinical Importance: Activation of the RAAS contributes to the pathophysiology of intrahepatic PH in dogs, suggesting that spironolactone may not only be effective for the treatment of ascites but also for the suppression of intrahepatic PH. K E Y W O R D S canine, chronic hepatitis, portal hypertension, primary hypoplasia of the portal vein, reninangiotensin-aldosterone system

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“…no. JK0088; Peninsula Laboratories International, Inc., San Carlos, CA, USA) was used to detect the concentration of ET-1 (21,22).…”

Section: Patientsmentioning

confidence: 99%

Risk factors for hypertensive retinopathy in a Chinese population with hypertension: The Beijing Eye study

Zhang

Zhao

et al. 2018

Exp Ther Med

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Hypertensive retinopathy (HRP) is a clinical feature and systemic manifestation of hypertension. There have been few reports on the risk factors for hypertensive retinopathy in China. The aim of the present study was to describe risk factors associated with HRP in a population-based sample of Chinese patients with hypertension in Beijing. The clinical data of 228 hypertensive patients was retrospectively studied, including 112 patients with retinopathy for the HRP group and 116 patients without retinopathy for the NO-HRP group. Basic clinical data and plasma clinical indicators of the two groups were compared. Logistic regression models were used to assess risk factors associated with HRP. Duration of hypertension, smoking habits, family history of hypertension, plasma level of endothelin-1 (ET-1) and systolic and diastolic blood pressure were significantly increased in the HRP group compared with the NO-HRP group (P<0.05). No significant differences were identified between the two groups for other factors. Logistic regression models indicated that hypertension duration (P<0.001, 95% CI: 0.962-0.988) and ET-1 level (P<0.001, 95% CI: 1.144-1.278) were significantly associated with HRP. The diagnostic threshold of ET-1 to diagnosis HRP was 43.5 ng/l. Of the factors studied, longer hypertension duration and elevated ET-1 level were identified to be risk factors for HRP in patients with hypertension from Beijing. Detecting the plasma level of ET-1 in patients with hypertension may be a useful diagnostic indicator for HRP.

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Effect of Breed on Plasma Endothelin‐1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs

Cited by 9 publications

References 54 publications

Genome wide association study of 40 clinical measurements in eight dog breeds

Genome wide association study of 40 clinical measurements in eight dog breeds

Plasma renin activity and aldosterone concentration in dogs with acquired portosystemic collaterals

Risk factors for hypertensive retinopathy in a Chinese population with hypertension: The Beijing Eye study

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