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Research article - Peer-reviewed, 2021

Polymorphisms in the serotonin transporter gene and circulating concentrations of neurotransmitters in Cavalier King Charles Spaniels with myxomatous mitral valve disease

Reimann, Maria J.; Fredholm, Merete; Cremer, Signe E.; Christiansen, Liselotte B.; Meurs, Kathryn M.; Moller, Jacob E.; Haggstrom, Jens; Lykkesfeldt, Jens; Olsen, Lisbeth H.


Background The neurotransmitter serotonin (5-HT) affects valvular degeneration and dogs with myxomatous mitral valve disease (MMVD) exhibit alterations in 5-HT signaling. In Maltese dogs, 3 single nucleotide polymorphisms (SNPs) in the 5-HT transporter (SERT) gene are suggested to associate with MMVD. Hypothesis/Objectives Determine the association of SERT polymorphisms on MMVD severity and serum 5-HT concentration in Cavalier King Charles Spaniels (CKCS). Additionally, investigate the association between selected clinical and hematologic variables and serum 5-HT and assess the correlation between HPLC and ELISA measurements of serum 5-HT. Animals Seventy-one CKCS (42 females and 29 males; 7.8 [4.7;9.9] years (median [Q1;Q3])) in different MMVD stages. Methods This prospective study used TaqMan genotyping assays to assess SERT gene polymorphisms. Neurotransmitter concentrations were assessed by HPLC and ELISA. Results TaqMan analyses identified none of the selected SERT polymorphisms in any of the CKCS examined. Serum 5-HT was associated with platelet count (P < .001) but not MMVD severity, age or medical therapy and did not correlate with serum concentration of the 5-HT metabolite, 5-hydroxyindoleacetic acid. The ELISA serum 5-HT correlated with HPLC measurements (rho = .87; P < .0001) but was lower (mean difference = -22 ng/mL; P = .02) independent of serum 5-HT concentration (P = .2). Conclusions and Clinical Importance Selected SERT SNPs associated with MMVD in Maltese dogs were not found in CKCS and only platelet count influenced serum 5-HT concentration. These SNPs are unlikely to be associated with MMVD pathophysiology or serum 5-HT concentration in CKCS. HPLC and ELISA serum 5-HT demonstrated good correlation but ELISA systematically underestimated 5-HT.


dogs; ELISA; genetic variation; heart disease; HPLC; serum serotonin

Published in

Journal of Veterinary Internal Medicine
2021, volume: 35, number: 6, pages: 2596-2606
Publisher: WILEY

Authors' information

Reimann, Maria J.
University of Copenhagen
Fredholm, Merete
University of Copenhagen
Cremer, Signe E.
University of Copenhagen
Christiansen, Liselotte B.
University of Copenhagen
Meurs, Kathryn M.
University of North Carolina
Moller, Jacob E.
University of Copenhagen
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Lykkesfeldt, Jens
University of Copenhagen
Olsen, Lisbeth H.
University of Copenhagen

UKÄ Subject classification

Clinical Science

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