Hyperhomocysteinemia in Greyhounds and Its Association with Hypofolatemia and Other Clinicopathologic Variables

Overview

Journal J Vet Intern Med

Specialties General Medicine
Veterinary Medicine

Date 2016 Nov 20

PMID 27864850

Citations 9

Authors

R M Heilmann

N Grutzner

M C Iazbik

R Lopes

C S Bridges

J S Suchodolski

C G Couto

J M Steiner

Affiliations

Soon will be listed here.

Abstract

Background: Folate and cobalamin are essential cofactors for homocysteine (HCY) metabolism. Hyperhomocysteinemia, a multifactorial condition, may reflect B vitamin deficiency and is associated with increased risk of cardiovascular disease, thrombosis, and neurodegenerative and chronic gastrointestinal diseases in humans. Hyperhomocysteinemia has been reported in Greyhounds with suspected chronic enteropathy.

Objectives: To evaluate the frequencies of and the association between hypofolatemia and hyperhomocysteinemia in Greyhounds.

Animals: Data and serum samples from 559 Greyhounds.

Methods: Nested case-control study. The frequency of hypofolatemia in Greyhounds was determined by a laboratory database search. The relationship between hyperhomocysteinemia (measured by gas chromatography-mass spectrometry) and hypocobalaminemia and hypofolatemia was evaluated, and its frequency compared between healthy Greyhounds and Greyhounds with thrombosis or chronic diarrhea.

Results: Hypofolatemia was identified in 172 of 423 (41%) Greyhounds and was more common in hypo- than in normocobalaminemic dogs (49% vs. 35%; P = .0064). Hyperhomocysteinemia was detected in 53 of 78 (68%) of Greyhounds, being more common in hypo- than in normofolatemic dogs (88% vs. 59%; P = .0175). All healthy Greyhounds, 21 of 30 (70%) of dogs with chronic diarrhea and 6 of 8 (75%) of those with thrombosis, were hyperhomocysteinemic. Serum HCY concentrations were inversely correlated with serum folate concentration (ρ = -0.28; P = .0386) and were positively associated with serum albumin concentration (ρ = 0.66; P = .0022).

Conclusions And Clinical Relevance: Hyperhomocysteinemia occurs frequently in the Greyhound population. Its association with hypofolatemia suggests decreased intracellular availability of B vitamins, but the functional implications warrant further investigation. Hyperhomocysteinemia in Greyhounds potentially may serve as a spontaneous canine model to further investigate hyperhomocysteinemia in humans.

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References

Cullen C, Carter G, Weiss M, Grant P, Saperstein D . Hypohomocysteinemia: a potentially treatable cause of peripheral neuropathology?. Phys Med Rehabil Clin N Am. 2012; 23(1):59-65, x. DOI: 10.1016/j.pmr.2011.11.001. View

Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J, Dierkes J . DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med. 2003; 41(11):1392-403. DOI: 10.1515/CCLM.2003.214. View

Baines E, Watson P, Stidworthy M, Herrtage M . Gross pulmonary thrombosis in a greyhound. J Small Anim Pract. 2001; 42(9):448-52. DOI: 10.1111/j.1748-5827.2001.tb02499.x. View

Breda S, Giordano A, Pengo G, DallAra P, Rossi G, Bo S . Association between hypocobalaminaemia and hyperhomocysteinaemia in dogs. Vet Rec. 2013; 172(14):365. DOI: 10.1136/vr.101171. View

Innera M . Cutaneous vasculitis in small animals. Vet Clin North Am Small Anim Pract. 2012; 43(1):113-34. PMC: 7124213. DOI: 10.1016/j.cvsm.2012.09.011. View

Folstein M, Liu T, Peter I, Buell J, Buel J, Arsenault L . The homocysteine hypothesis of depression. Am J Psychiatry. 2007; 164(6):861-7. DOI: 10.1176/ajp.2007.164.6.861. View

Lentz S, Sadler J . Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine. J Clin Invest. 1991; 88(6):1906-14. PMC: 295763. DOI: 10.1172/JCI115514. View

Aminzadeh M, Gollapudi P, Vaziri N . Effect of nephrotic syndrome on homocysteine metabolism. Nephrol Dial Transplant. 2010; 26(4):1244-7. DOI: 10.1093/ndt/gfq551. View

Stabler S, Marcell P, Podell E, Allen R . Quantitation of total homocysteine, total cysteine, and methionine in normal serum and urine using capillary gas chromatography-mass spectrometry. Anal Biochem. 1987; 162(1):185-96. DOI: 10.1016/0003-2697(87)90026-1. View

10.

Scazzone C, Bono A, Tornese F, Arsena R, Schillaci R, Butera D . Correlation between low folate levels and hyperhomocysteinemia, but not with vitamin B12 in hypertensive patients. Ann Clin Lab Sci. 2014; 44(3):286-90. View

11.

Hortin G, Seam N, Hoehn G . Bound homocysteine, cysteine, and cysteinylglycine distribution between albumin and globulins. Clin Chem. 2006; 52(12):2258-64. DOI: 10.1373/clinchem.2006.074302. View

12.

Grutzner N, Suchodolski J, Steiner J . Relationship between cobalamin-dependent metabolites and both serum albumin and alpha1 -proteinase inhibitor concentrations in hypocobalaminemic dogs of 7 different breeds. Vet Clin Pathol. 2014; 43(4):561-6. DOI: 10.1111/vcp.12204. View

13.

Fayos M, Couto C, Iazbik M, Wellman M . Serum protein electrophoresis in retired racing Greyhounds. Vet Clin Pathol. 2005; 34(4):397-400. DOI: 10.1111/j.1939-165x.2005.tb00068.x. View

14.

Erzin Y, Uzun H, Celik A, Aydin S, Dirican A, Uzunismail H . Hyperhomocysteinemia in inflammatory bowel disease patients without past intestinal resections: correlations with cobalamin, pyridoxine, folate concentrations, acute phase reactants, disease activity, and prior thromboembolic complications. J Clin Gastroenterol. 2008; 42(5):481-6. DOI: 10.1097/MCG.0b013e318046eab0. View

15.

Papa A, De Stefano V, Danese S, Chiusolo P, Persichilli S, Casorelli I . Hyperhomocysteinemia and prevalence of polymorphisms of homocysteine metabolism-related enzymes in patients with inflammatory bowel disease. Am J Gastroenterol. 2001; 96(9):2677-82. DOI: 10.1111/j.1572-0241.2001.04127.x. View

16.

Surman S, Couto C, DiBartola S, Chew D . Arterial blood pressure, proteinuria, and renal histopathology in clinically healthy retired racing greyhounds. J Vet Intern Med. 2012; 26(6):1320-9. DOI: 10.1111/j.1939-1676.2012.01008.x. View

17.

Rodgers G, Kane W . Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator. J Clin Invest. 1986; 77(6):1909-16. PMC: 370551. DOI: 10.1172/JCI112519. View

18.

Goodwin L, Goggs R, Chan D, Allenspach K . Hypercoagulability in dogs with protein-losing enteropathy. J Vet Intern Med. 2011; 25(2):273-7. DOI: 10.1111/j.1939-1676.2011.0683.x. View

19.

Vilar P, Couto C, Westendorf N, Iazbik C, Charske J, Marin L . Thromboelastographic tracings in retired racing greyhounds and in non-greyhound dogs. J Vet Intern Med. 2008; 22(2):374-9. DOI: 10.1111/j.1939-1676.2008.0061.x. View

20.

Zaldivar-Lopez S, Marin L, Iazbik M, Westendorf-Stingle N, Hensley S, Couto C . Clinical pathology of Greyhounds and other sighthounds. Vet Clin Pathol. 2011; 40(4):414-425. PMC: 3816276. DOI: 10.1111/j.1939-165X.2011.00360.x. View