Polymorphisms in the canine glucocorticoid receptor alpha gene (NR3C1α)
| Autor: | Katrina L. Mealey, Rance K. Sellon, Michael H. Court, Ana Petra Costa, Neal S. Burke |
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| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Pharmacology Genetics Polymorphism Genetic General Veterinary In silico Single-nucleotide polymorphism DNA Biology 03 medical and health sciences Exon 030104 developmental biology Glucocorticoid receptor Dogs Receptors Glucocorticoid Gene Expression Regulation Coding region Animals Genetic variability Allele Gene |
| Zdroj: | Journal of veterinary pharmacology and therapeutics. 39(1) |
| ISSN: | 1365-2885 |
| Popis: | Corticosteroids are one of the most extensively used class of therapeutic agents in dogs. In human patients, response to corticosteroid therapy has been correlated with the presence of certain polymorphisms of the glucocorticoid receptor gene (NR3C1). Depending on the polymorphism present, patients may show either increased sensitivity to glucocorticoid-induced adverse effects or resistance to their therapeutic effects. Because response to corticosteroid therapy in dogs can also be variable and unpredictable, we hypothesized that genetic variability exists in the canine NR3C1 gene. The aim of this study was to sequence the coding regions of the canine NR3C1 gene in a representative sample of dogs. Samples from 97 dogs from four previously identified genetic groupings of domestic breeds (Asian/Ancient, Herding, Hunting, and Mastiff) were sequenced and evaluated. Four exons contained polymorphisms and four exons showed no variation from the reference sequence. A total of six single nucleotide polymorphisms (SNPs) were identified including four synonymous SNPs and two nonsynonymous SNPs (c.811A>T and c.2111T>C). No dogs were homozygous for either variant allele, while 23 dogs were heterozygous for the c.811A>T allele and 2 were heterozygous for c.2111T>C allele. The amino acid changes caused by c.811A>T (serine to cysteine) and c.2111T>C (isoleucine to threonine) were both predicted by in silico analysis to be ‘probably damaging’ to structure and function of the resulting protein. We conclude that NR3C1 polymorphisms occur in dogs and may cause individual variation in response to corticosteroid therapy. |
| Databáze: | OpenAIRE |
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