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

对患有原发性免疫性血小板减少症的可卡犬NR3C1a糖皮质激素受体基因中的单核苷酸多态性进行研究

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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.

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