STONE STUDY PARTICIPANTS NEEDED!

RENOWNED DALMATIAN URINARY STONE EXPERT, DR JOSEPH BARTGES TO CONDUCT RESEARCH STUDY

DCA Chair of the Health and Research Study Group on Stones, Kathy McCoubrey recently released a request for participants in a study to be conducted by world renowned stone expert Dr. Joseph Bartges of the University of Tennessee Veterinary Medical Center. The preliminary study will require 15 pairs of male Dalmatians. The pair must be littermates with one of them a confirmed urate stone former and the other never having formed stones. The study is actually a small part of a larger study, one in which Dr. Bartges has generously offered to include DCA. It involves blood samples for DNA analysis and will attempt to answer the question "even though all Dalmatians have high uric acid, is there a genetic component related to why some of them form urate stones but most, including littermates, do not?"

FAQ'S

  1. What hypotheses are being tested?
    All Dalmatians are predisposed to high levels of uric acid but only a few progress to the stage of becoming urate stone formers. Therefore, there must be other unknown factors involved. Thus, it would be prudent to screen the entire genome for differences between urate stone-forming and non stone-forming Dalmatians. To limit genetic diversity, this preliminary study would involve 15 pairs of littermate siblings, one who has a history of forming urate stones and one who does not.

  2. What testing will be done?
    A simple blood draw will allow a complex analysis to determine differences between the urate stone-former and the unaffected sibling.

  3. Where will the testing be done? The SNP (single nucleotide polymorphism) chips will be processed at the University of Tennessee through the Affymetrix Core Facility.

  4. Is there a cost to participate?
    While the tests will actually be quite costly, the Dalmatian Club of America Foundation is underwriting the expense.

  5. What information will be needed to participate?
    At this time, we are trying to identify at least 15 matched pairs of littermates. Once the list of possible participants is passed on to Dr. Bartges, he will contact the owners to get any further information he requires.

Dr. Bartges has stated that "if high uric acid excretion is the sole cause of urate stone formation then, at least theoretically, all Dalmatians should form urate stones". He expressed his concern that "the removal of the gene for high uric acid as the 'cause' of urate stone formation in Dalmatians may result in formation of other stone types in those Dalmatians that carry whatever gene(s) predispose them to stone formation." His opinion is that decreasing uric acid will likely help with decreasing urate stone formation in Dalmatians, "but perhaps not stone formation in general. It might do nothing to eliminate stones of another composition such as calcium oxalate, which do not dissolve."

Dr. Bartges further stated, "Without hyperuric aciduria (high uric acid in urine), formation of urate stones is unlikely in most patients.... However, there are patients that form urate stones without high blood levels of uric acid (idiopathic urate stone formation)"

Interested participants should contact Traci Tepke by Email.

UPDATE January 23, 2012

"We were able to use data from 20 sibling pairs - one member of each pair was a known stone former (urate) and the other was a known non-stone former. Only male sibling pairs were used. There were 147,000 SNPs evaluated and of those 874 were found to be different between the stone-formers and non-stone formers. 220 of these had less frequency -bringing the total to 654 possibilities. In assessing whether these may have some importance or not we were able to narrow it to 7 strong candidates and of these there were 3 that involved a coding region and of these, 2 seemed to clinically/physiologically make sense:

  • SLC8A1: a solute carrier family 1 (sodium/calcium exchanger), member 1 - on chromosome 17
  • CACNA1C: a calcium channel, voltage-dependent, L type, alpha 1C subunit on chromosome 27

The SLC8A1 (sodium:calcium exchanger on chromosome 17) is most interesting (SNP location: 35183560). Other SLC genes have been associated with high uric acid levels. Specifically, SLC2A9 variants may be responsible for high uric acid levels in Dalmatians and SLC22A12 is involved with uric acid diseases in humans. In a study of human familial juvenile hyperuricemic nephropathy, the SLC8A1 region was identified. To pursue this a bit further - we believe that we would need to acquire an additional 10 sibling pair samples or 20 non-sibling pair samples - stone formers and nonstone formers - males only. We may be able to determine the relevance of the above findings. If we do 10 sibling pairs - it would be worth running them on the Affymetric chip. If this can be proven to be significant (as we don't have statistical significance at this point - but are close in a convincing way due to the low numbers of pairs), a more rapid and less expensive PCR test could be used to evaluate the prevalence of the SNP in a larger population and to determine its relevance to stone formation in Dalmatians."

Respectfully submitted,
Joe

Joe Bartges, DVM, PhD, DACVIM, DACVN
Professor of Medicine and Nutrition
The Acree Endowed Chair of Small Animal Research
C247 Veterinary Teaching Hospital
Department of Small Animal Clinical Sciences
College of Veterinary Medicine
The University of Tennessee

This page last updated on April 23, 2015

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