Evangelista Gabriela C L, Hwang Julianne K, Broughton-Neiswanger Liam E, Carlo Reis Emily C, Court Michael H, Mealey Katrina A, Villarino Nicolas F
Veterinary Department, Federal University of Viçosa, Viçosa, Brazil.
Department of Veterinary Clinical Sciences College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
J Vet Intern Med. 2025 Jul-Aug;39(4):e70136. doi: 10.1111/jvim.70136.
The protein apoptosis inhibitor of macrophages (AIM) is involved in kidney repair. An AIM (fAIM) genetic variant in cats resulting in a domain duplication might abrogate fAIM's protective effect on kidney function.
To confirm that the domain duplication previously described in fAIM results from an exon duplication at the genomic level and to determine if cats with chronic kidney disease (CKD) harboring the variant fAIM allele are at higher risk for a decline in renal function relative to fAIM wild-type cats.
Medical records (n = 172) and genomic DNA samples (n = 100) from cats presented to Washington State University and having a diagnosis of CKD were analyzed.
Sequencing and PCR were used to determine fAIM genotype. Based on serum creatinine (SCr) concentrations, cats were phenotyped according to IRIS CKD staging. The phenotype-genotype association was tested using Fisher's exact test.
The 4-domain variant of fAIM was confirmed to be a result of exon 3 duplication and is present in 62% of the DNA samples from cats. Medical records of cats (n = 50) with CKD met the inclusion criteria. Cats homozygous for the exon 3 fAIM variant allele are more likely to have worse IRIS stage (p = 0.01) and more likely to have experienced renal function deterioration (increasing SCr concentration) than fAIM wild-type cats (p = 0.03).
The fAIM homozygous variant genotype is associated with declining kidney function in cats with CKD, presumably from deficient fAIM-mediated renal tubular repair.
巨噬细胞凋亡抑制蛋白（AIM）参与肾脏修复。猫体内一种导致结构域重复的AIM（fAIM）基因变异可能会消除fAIM对肾功能的保护作用。
确认先前描述的fAIM结构域重复是由基因组水平的外显子重复引起的，并确定携带fAIM变异等位基因的慢性肾病（CKD）猫相对于fAIM野生型猫肾功能下降的风险是否更高。
分析了提交给华盛顿州立大学且被诊断为CKD的猫的病历（n = 172）和基因组DNA样本（n = 100）。
采用测序和聚合酶链反应（PCR）来确定fAIM基因型。根据血清肌酐（SCr）浓度，按照国际肾脏病学会（IRIS）CKD分期对猫进行表型分型。使用Fisher精确检验来测试表型-基因型关联。
fAIM的4结构域变异被确认为外显子3重复的结果，并且存在于62%的猫DNA样本中。符合纳入标准的CKD猫（n = 50）的病历。与fAIM野生型猫相比，外显子3 fAIM变异等位基因纯合的猫更有可能处于较差的IRIS分期（p = 0.01），并且更有可能经历肾功能恶化（SCr浓度升高）（p = 0.03）。
fAIM纯合变异基因型与CKD猫的肾功能下降有关，可能是由于fAIM介导的肾小管修复功能不足。
