Investigation of single-nucleotide polymorphisms in the NR3C1a glucocorticoid receptor gene in Cocker Spaniels with primary immune thrombocytopenia

J Vet Intern Med. 2022 Jul;36(4):1281-1286. doi: 10.1111/jvim.16468. Epub 2022 Jun 10.

Abstract

Background: In dogs, 6 single-nucleotide polymorphisms (SNPs) have been described in the glucocorticoid receptor gene NR3C1a, 2 of which were nonsynonymous SNPs in exons 2 and 8. The clinical importance of these SNPs is unknown.

Objectives: To investigate whether SNPs in NR3C1a are associated with clinical outcome in Cocker Spaniels with primary immune thrombocytopenia (pITP).

Animals: Twenty-four Cocker Spaniels with pITP presented to a referral center. Dogs were classified as slow (n = 11) or fast responders (n = 12) based on time required after initiating glucocorticoid treatment to achieve a platelet count >70 000/μL.

Methods: Deoxyribonucleic acid was extracted from stored blood samples before amplification by PCR and sequencing of exons 2 and 8 of NR3C1a. Associations between genotype and clinical response variables were investigated.

Results: Neither previously identified nonsynonymous SNPs were identified. The synonymous SNP NR3C1a:c.798C>T in exon 2 was found at an increased prevalence compared to a previous report. No difference was found in prevalence of any genotype at NR3C1a:c.798C>T between fast and slow responders (P = .70).

Conclusions and clinical importance: None of the previously reported nonsynonymous SNPs in exons 2 and 8 of the NR3C1a gene were detected in our cohort of Cocker Spaniels with pITP. The synonymous SNP NR3C1a:c.798C>T in exon 2 was reported at a higher frequency than previously, but was not associated with outcome measures that estimated responsiveness to glucocorticoids.

Keywords: canine; corticosteroids; genetics; immune-mediated; platelet.

MeSH terms

  • Animals
  • Dog Diseases* / epidemiology
  • Dog Diseases* / genetics
  • Dogs
  • Glucocorticoids / therapeutic use
  • Polymorphism, Single Nucleotide
  • Purpura, Thrombocytopenic, Idiopathic* / genetics
  • Purpura, Thrombocytopenic, Idiopathic* / veterinary
  • Receptors, Glucocorticoid / genetics

Substances

  • Glucocorticoids
  • Receptors, Glucocorticoid

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