EXPRESS: Prevalence of the AIM exon 3 duplication variant, a putative biomarker associated with progression of kidney disease, in 1,000 cats

OBJECTIVES: A protein called 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 (CKD). Pilot studies suggest that homozygosity for this genetic alteration is present in about 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. METHODS: Genomic DNA from 1,000 client-owned cats archived in the PrIMe DNA Bank at Washington State University was analyzed by droplet digital PCR to determine AIM exon 3 copy number variation (CNV). Samples represented cats of any age, sex, neuter status, or clinical condition. Genotype frequencies were summarized with 95 % Wilson confidence intervals (95% CI), and genotype frequencies were tested for deviation from Hardy-Weinberg equilibrium (HWE) by χ² analysis. RESULTS: Of the 1,000 cats, 340 (34.0%; 95% CI 31.1-36.9) were homozygous wild-type (CVN2), 467 (46.7%; 95% CI 43.6-50.0) were heterozygous (CVN3), and 193 (19.3%; 95% CI 17.0-21.9) were homozygous for the variant (CVN4). Genotype frequencies deviate from Hardy-Weinberg equilibrium (χ² = 4.49, df = 1, p = 0.034). CONCLUSIONS AND RELEVANCE: Approximately one in five 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.