Dataset Information

DLA class II alleles and haplotypes are associated with risk for and protection from chronic hepatitis in the English Springer spaniel.

ABSTRACT: Chronic hepatitis (CH) is common in dogs in the United Kingdom. An increased prevalence of the disease is seen in the English Springer spaniel (ESS), and this breed suffer from a severe form with young to middle aged female dogs being predisposed. The disease shares histological features with those of human viral hepatitis, although the specific aetiological agent has not yet been identified. The aim of the current study was to investigate whether dog leucocyte antigen (DLA) class II alleles and haplotypes are associated with susceptibility/resistance to CH in the ESS. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1 and -DQB1 class II loci were performed in 66 ESSs with CH and 84 healthy controls. There was a significant difference in the distribution of the protective alleles DRB1*00501 (3.0% vs. 12.0%, odds ratio [OR] = 0.23, 95% confidence interval [CI] = 0.06-0.74) and DQB1*00501 (3.8% vs. 12.0%, OR = 0.29, 95% CI = 0.09-0.85) between cases and controls. The haplotype DLA-DRB1*00501/DQA1*00301/DQB1*00501 was present in 11.9% of controls and 3.0% of cases and was significantly associated with protection against disease development (OR = 0.26, 95% CI = 0.08-0.80). There was a significant difference in the distribution of the risk alleles DRB1*00601 (14.4% vs. 6.5%, OR = 2.40, 95% CI = 1.10-5.63) and DQB1*00701 (14.4% vs. 6.5%, OR = 2.40, 95% CI = 1.10-5.63) between cases and controls. A risk haplotype (DLA-DRB1*00601/DQA1*005011/DQB1*00701) was present in 14.4% of cases and 6.5% of controls and conferred an elevated risk of developing CH with an OR of 3.13 (95% CI = 1.20-8.26). These results demonstrate that DLA class II is significantly associated with risk and protection from developing CH in ESSs.

SUBMITTER: Bexfield NH

PROVIDER: S-EPMC3411618 | biostudies-other | 2012

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BACKGROUND: The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the MCP1 -362C and the MCP1 -2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the MCP1 gene in order to determine causal variants or haplotypes genetically and functionally. RESULTS: A 14 base-pair deletion in the first MCP1 intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR=0.84, CI 0.77-0.92, Pcorrected=0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR=0.78, CI 0.69-0.87, Pnominal=0.00002; adjusted Pglobal=0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the MCP1 mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P=0.02 and P=0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB. CONCLUSIONS: In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the MCP1 -362C allele alone (OR=0.78, CI 0.69-0.87 vs OR=0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.

Dataset Information

DLA class II alleles and haplotypes are associated with risk for and protection from chronic hepatitis in the English Springer spaniel.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets