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

Tayler, Sarah; Hazuchova, Katarina; Riddle, Anna; Swann, James W; Glanemann, Barbara

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.

Citation

Tayler, S., Hazuchova, K., Riddle, A., Swann, J. W., & Glanemann, B. (2022). Investigation of single-nucleotide polymorphisms in the NR3C1a glucocorticoid receptor gene in Cocker Spaniels with primary immune thrombocytopenia. Journal of Veterinary Internal Medicine, https://doi.org/10.1111/jvim.16468

• Journal Article Type: Article
• Acceptance Date: May 27, 2022
• Online Publication Date: Jun 10, 2022
• Publication Date: 2022
• Deposit Date: Jul 7, 2022
• Publicly Available Date: Jul 12, 2022
• Print ISSN: 0891-6640
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/jvim.16468
• Keywords: canine, corticosteroids, genetics, immune-mediated, platelet