Egyptian Mau Urate Stone Genetic Study

The high odds ratios in the Egyptian Mau to develop urate stones may suggest a genetic cause to the predisposition for urate stones.

Introduction

Uroliths (stones) are a relatively common problem in cats, accounting for approximately 15% to 23% of all cases of feline lower urinary tract disease (FLUTD)1-3. The stones are predominately found in the lower urinary tract, most specifically in the bladder. The two most common types of urolith identified in cats are struvite (magnesium ammonium phosphate hexa-hydrate) and calcium oxalate4-8. Urate uroliths are the third most common urolith type in cats, accounting for approximately 6% to 9% of feline uroliths submitted for analysis.14,15 Unlike struvite and calcium oxalate uroliths, the incidence of urate uroliths seems to have remained stable over the past 2 decades.

In cats, urate uroliths (stones) are predominantly associated with liver disease, specifically portosystemic vascular anomalies. Idiopathic urate uroliths may occur in animals without liver disease.10 Urate stones in cats are found almost exclusively in the bladder, and males and females are equally affected.15 Ammonium urate, a salt of uric acid, is the most common substance in urate stones.9 The pathogenesis in cats (with the exception of portosystemic vascular anomalies) remains unclear16, thus we do not know why cats get the urate bladder stones.

The Egyptian Mau have been shown to be significantly predisposed to urate stones in several studies.11-13 Often described as an odds ratio (OR), Egyptian maus have are shown to have an odds ratio (OR) = 118.95, meaning a mau will get stones 118x more likely than any other cat.

In a second, study12, the risk of ammonium urate stones in Egyptian maus was OR = 94.5. In 2012, Egyptian Maus were demonstrated to have an OR = 44.41 for urate stones.13  In each study, the results were highly significant.

Genetic Study

We are performing association and whole genome sequencing studies to identify the causal DNA variant for urate stones in the Egyptian Mau cat breed.

How can you help?

We need DNA samples from your cats, pedigrees, and a definitive diagnosis of the type of stones in your cat.

This is a urate stone study!

Cats can get struvite and calcium oxalate stones too. Incorrect diagnosis will compromise the study!

**All previous samples are still in the lab, we may contact you to confirm information on the type of stones.

For genome-wide association study (GWAS) approach (DNA arrays):

  1. We need buccal swab samples from Egyptian Mau cats with stones, AND from their normal parents and siblings. Each case (cat with stones) needs a matching control (close relative without stones – older the better).
  2. Buccal swab instructions and the submission form can be found here. Once we have found the gene and the DNA variant, DNA from the buccal swabs will be used to type additional cats to verify the accuracy of our discovery and to develop a genetic test.
  3. DNA array studies generally require 20 cases and 20 control cats from the same breed and population.

For potential whole genome sequencing (WGS):

  1. We need 6 ml of EDTA whole blood from trios of cats – two parents and an offspring – where one individual has had stones.
  2. Instructions for collection and shipping are found here.
  3. Gonads can be submitted for DNA isolation as well. If you have a cat that is to be altered / desexed/ neutered or spayed – we can use these tissues for the projects as well (WGS or GWAS). See instructions here.
  4. Tissues from a cat that you have recently had to euthanized or has passed can also be submitted. We are sorry for your loss – but maybe this kitty can contribute to science for other cats. Instructions for tissue submissions are here.

Funding

Donations of funds for the study will increase the research priority. Each cat genome sequence costs ~$1,000.  A DNA array projects costs about the same. Additionally, we will require funds for data analyses, DNA variant testing and personnel time.

Donations can be made – tax deductible – at the MU GiveDirect site for the 99 Lives Project for the Lyons Laboratory: https://mizzougivedirect.missouri.edu/Item.aspx?item_id=251

Please add – “Lyons lab – Egyptian Mau Stone Project” –  in the comments.

References

  1. Lekcharoensuk C, Osborne CA, Lulich JP. Epidemiologic study of risk factors for lower urinary tract diseases in cats. J Am Vet Med Assoc. 2001;218:1429–1435.
  2. Buffington CA, Chew DJ, Kendall MS, et al. Clinical evaluation of cats with nonobstructive urinary tract diseases. J Am Vet Med Assoc. 1997;210:46–50.
  3. Gerber B, Boretti FS, Kley S, et al. Evaluation of clinical signs and causes of lower urinary tract disease in European cats. J Small Anim Pract. 2005;46:571–577.
  4. Houston DM, Moore AE, Favrin MG, Hoff B. Canine urolithiasis: A look at over 16 000 urolith submissions to the Canadian Veterinary Urolith Centre from February 1998 to April 2003. Can Vet J. 2004;45:225–230.
  5. Houston DM, Moore AEP. Canine and feline urolithiasis: Examination of over 50 000 urolith submissions to the Canadian veterinary urolith centre from 1998 to 2008. Can Vet J. 2009;50:1263–1268.
  6. Osborne CA, Lulich JP, Kruger JM, Ulrich LK, Koehler LA. Analysis of 451 891 canine uroliths, feline uroliths, and feline urethral plugs from 1981 to 2007: Perspectives from the Minnesota Urolith Center. Vet Clin North Am Small Anim Pract. 2009;39:183–197.
  7. Picavet P, Detilleux J, Verschuren S, et al. Analysis of 4495 canine and feline uroliths in the Benelux. A retrospective study: 1994–2004. J Anim Physiol Anim Nutr. 2007;91:247–251.
  8. Cannon AB, Westropp JL, Ruby AL, Kass PH. Evaluation of trends in urolith composition in cats: 5,230 cases (1985–2004) J Am Vet Med Assoc. 2007;231:570–576.
  9. Bartges JW, Osborne CA, Lulich JP, et al. Canine urate urolithiasis: etiopathogenesis, diagnosis, and management. Vet Clin North Am Small Anim Pract 1999;29(1):161-191.
  10. McCue J, Langston C, Palma D, Gisselman K. Urate urolithiasis. Compend Contin Educ Vet. 2009 Oct;31(10):468-75; quiz 475. PMID: 20180216
  11. Houston DM, Vanstone NP, Moore AE, Weese HE, Weese JS. Evaluation of 21 426 feline bladder urolith submissions to the Canadian Veterinary Urolith Centre (1998-2014). Can Vet J. 2016 Feb;57(2):196-201. PubMed PMID: 26834273; PubMed Central PMCID: PMC4713001.
  12. Appel SL, Houston DM, Moore AE, Weese JS. Feline urate urolithiasis. Can Vet J. 2010 May;51(5):493-6. PubMed PMID: 20676290; PubMed Central PMCID: PMC2857427.
  13. Albasan H, Osborne CA, Lulich JP, Lekcharoensuk C. Risk factors for urate uroliths in cats. J Am Vet Med Assoc. 2012;240:842–847.
  14. Houston DM, Moore AEP, Favrin MG, et al. Feline urethral plugs and bladder uroliths: a review of 5484 submissions (1998-2003). Can Vet J 2003;44:974-977.
  15. Cannon AB, Westropp JL, Ruby AL, et al. Evaluation of trends in urolith composition in cats: 5,230 cases (1985-2004). JAVMA 2007;231:570-576.
  16. Osborne CA. Diseases of the lower urinary tract. In: Finco DR, Osborne CA, eds. Canine and Feline Urology and Nephrology. Baltimore: Lippincott Williams and Wilkins; 1995:822-833.