Authors K. Hazuchova (1), R. Gostelow (1), S.J.M. Niessen (1), D.B. Church (1), M. Boursnell (2), B. Catchpole (3), Y. Forcada (1)
Affiliations 1. Department of Clinical Science and Services, The Royal Veterinary College, United Kingdom; 2. Animal Health Trust, Newmarket, United Kingdom; 3. Department of Pathobiology and Population Sciences, The Royal Veterinary College, United Kingdom
Presentation Type Poster
Abstract
Diabetes mellitus (DM) in cats resembles type 2 DM in humans. A genome-wide association study of DM in Domestic Shorthair (DSH) cats identified 3 single nucleotide polymorphisms (SNPs) located at the end of chromosome A3. The ACP1 gene, coding for a protein tyrosine phosphatase involved in insulin signalling, is in close proximity to these SNPs and was selected for further investigation as a candidate diabetes susceptibility gene.
The coding sequence for the ACP1 gene was identified in the cat genome assembly and Softberry ® software was used for promoter prediction. Gene-specific primers were designed to sequence the 6 exons and putative promoter using Primer-BLAST. Genomic DNA from well-phenotyped diabetic DSH cats (≥3 months on insulin, IGF-112 years, normoglycaemic) extracted from EDTA-blood was used for PCR and subsequent Sanger sequencing. Allele frequencies for identified SNPs were compared between diabetics and controls (Chi-square; significance pC; ACP1:c.-344C>T; ACP1:c.-378G>A; ACP1:c.-420G>C; ACP1:c.-4452G>C; ACP1:c.-693T>G). A case-control study (15 diabetics, 30 controls) revealed that the A-allele of c.-227A>C (p=0.00007), G-allele of c.-378G>A (p=0.00001), G-allele of c.-420G>C (p=0.02) and G-allele of c.-452G>C (p=0.0001) were significantly associated with DM. 9/15 diabetics and 6/30 controls were homozygous for the DM-associated haplotype (p=0.007).
Given the interaction of ACP1 with the insulin receptor, the potential functional impact of SNPs within the putative promoter of the ACP1 gene warrants further investigation.