Prevalence of the AIM exon 3 duplication variant, a putative biomarker associated with progression of kidney disease, in 1000 cats.

ObjectivesA protein called apoptosis inhibitor of macrophages (AIM) helps clear waste from the kidney tubules. Some domestic cats harbor a duplication of exon 3 in the AIM gene, producing a four-domain AIM protein that includes an additional scavenger receptor cysteine-rich subunit. This variant has been associated with increased risk of chronic kidney disease. Pilot studies suggest that homozygosity for this genetic alteration is present in approximately 20% of the cat population. The objective of the current study was to determine the prevalence of the wild-type, heterozygous and homozygous variant AIM exon 3 genotypes in a large population of domestic cats.MethodsGenomic DNA from 1000 client-owned cats archived in the Program in Individualized Medicine DNA Bank at Washington State University was analyzed by droplet digital PCR to determine AIM exon 3 copy number variation. Samples represented cats of any age, sex, neuter status or clinical condition. Genotype frequencies were summarized with 95% Wilson confidence intervals (CIs) and genotype frequencies were tested for deviation from Hardy-Weinberg equilibrium using χ2 analysis.ResultsOf the 1000 cats, 340 (34.0%, 95% CI 31.1-36.9) were homozygous wild-type (CNV2), 467 (46.7%, 95% CI 43.6-50.0) were heterozygous (CNV3) and 193 (19.3%, 95% CI 17.0-21.9) were homozygous for the variant (CNV4). Genotype frequencies deviate from Hardy-Weinberg equilibrium (χ2 = 4.49, degrees of freedom = 1; P = 0.034).Conclusions and relevanceApproximately 1/5 cats were homozygous for the AIM exon 3 duplication, and nearly half harbored one copy of the variant allele. This genetic alteration is not restricted to a single breed or type. Given the potential role of this variant in feline kidney disease, the results of this study justify further investigations using genetically confirmed and geographically diverse populations to better define global allele distributions and potential breed predispositions.