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Polymorphisms in the canine glucocorticoid receptor alpha gene ( NR 3C1α)
Author(s) -
Costa A.,
Sellon R. K.,
Court M.,
Burke N. S.,
Mealey K. L.
Publication year - 2016
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12241
Subject(s) - nonsynonymous substitution , single nucleotide polymorphism , glucocorticoid receptor , biology , allele , genetics , glucocorticoid , exon , gene , genetic variation , microbiology and biotechnology , endocrinology , genotype , genome
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 ( NR 3C1). 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 NR 3C1 gene. The aim of this study was to sequence the coding regions of the canine NR 3C1 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 ( SNP s) were identified including four synonymous SNP s and two nonsynonymous SNP s (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 NR 3C1 polymorphisms occur in dogs and may cause individual variation in response to corticosteroid therapy.