Genetic link to type 2 diabetes in Burmese cats in New Zealand

Abstract

AIM: To investigate, in a pilot study, a possible genetic component to type 2 diabetes mellitus (T2D) in Burmese cats in New Zealand by analysing pedigree data. METHODS: Pedigrees were obtained for 305 Burmese cats living in New Zealand; diabetes was diagnosed in 19 of these due to presence of polyuria and polydipsia, persistent concentrations of glucose in plasma >16 mmol/L and glucosuria prior to insulin treatment. Pedigrees were also submitted for 16 cats with no clinical signs of T2D. The remaining 270 cats were unobserved relatives of these individuals. Inbreeding coefficients and heritability were calculated, and a single major locus model segregation analysis was conducted using pedigree analysis software. RESULTS: Nineteen cats were diagnosed with T2D. Males (n = 14) and females (n = 5) were both affected, suggesting that the gene or genes causing diabetes are autosomal rather than sex-linked. Examination of the pedigree revealed few signs of fully penetrant dominant gene action: diabetes was ostensibly rarely seen in sequential generations and nearly always skipped at least one and often more generations; apparently unaffected offspring of apparently unaffected parents sometimes produced affected progeny. The mean relatedness of the affected animals within the core pedigree (16 diabetic cats) was 0.049, and mean inbreeding 0.033. Based on 100,000 permutations of the trait values, the expected relatedness of a random sample of 16 animals taken from the phenotyped animals would be 0.013 (SD 0.007) (permutation p = 0.0009). The observed inbreeding was also significant (permutation p= 0.02). Heritability was estimated to be 9 (95% CI = 0-57)% assuming all animals with unknown status were unaffected. The best fitting genetic model was a major gene model with dominant expression with the risk allele frequency at 15% with 60% penetrance. CONCLUSIONS: In this pilot study the increased inbreeding in the cases, lack of likely sampling bias, the increased frequency of T2D in Burmese, and small number of breed founders are consistent with the involvement of a major locus in diabetes in Burmese cats with a significant risk allele prevalence. However, low case numbers meant this could not be unambiguously confirmed. A genome-wide association study may be useful for investigating the genetic cause of T2D.