Association analysis of non-synonymous polymorphisms of interleukin-4 receptor-α and interleukin-13 genes in canine atopic dermatitis

Interleukin-4 (IL4) and interleukin-13 (IL13) are involved in the initial response of T helper 2 lymphocytes through the activation of the IL4 receptor alpha (IL4RA), which is a common receptor chain for these cytokines. In humans, several single-nucleotide polymorphisms (SNPs) identified in the IL4...

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Bibliographic Details
Published in:Journal of Veterinary Medical Science 2020, Vol.82(9), pp.1253-1259
Main Authors: TANAKA, Kazuaki, YAMAMOTO-FUKUDA, Misaki, TAKIZAWA, Tatsuya, SHIMAKURA, Hidekatsu, SAKAGUCHI, Masahiro
Format: Article
Language:English
Subjects:
Alleles
Amino acid substitution
Animals
Association analysis
Atopic dermatitis
Biochemistry
canine atopic dermatitis
Cell activation
Cytokines
Dermatitis
Dermatitis, Atopic - genetics
Dermatitis, Atopic - veterinary
Dog Diseases - genetics
Dogs
Gene polymorphism
Genetic Predisposition to Disease
Genotype
Interleukin 1
Interleukin 13
Interleukin 4
Interleukin 4 receptors
Interleukin-13 - genetics
interleukin-4 receptor
Lymphocytes
Lymphocytes T
Polymerase chain reaction
Polymorphism, Single Nucleotide
Receptors, Interleukin-4 - genetics
Restriction fragment length polymorphism
Single-nucleotide polymorphism
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Summary:Interleukin-4 (IL4) and interleukin-13 (IL13) are involved in the initial response of T helper 2 lymphocytes through the activation of the IL4 receptor alpha (IL4RA), which is a common receptor chain for these cytokines. In humans, several single-nucleotide polymorphisms (SNPs) identified in the IL4R and in interleukin coding genes were associated with atopic disorders. However, the association between canine IL4R polymorphisms and atopic disorders has not been investigated yet. This study aimed to determine the associations between four non-synonymous SNPs and canine atopic dermatitis (CAD) in shiba inu and miniature dachshund populations. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to genotype four polymorphisms of canine IL4R and IL13 in 34 shiba inu and 19 miniature dachshund patients with CAD, as well as 29 shiba inu and 39 miniature dachshund patients without the condition. Results from miniature dachshunds revealed a potential association between the presence of minor A allele rs24378020 and CAD (odds ratio, 0.10; 95% confidence interval, 0.01–0.85; Poriginal=0.0062). This CAD resistance allele led to an amino acid substitution (Arg688Cys) that could impair IL4 and IL13 signaling. In shiba inu patients, rs24378020 was fixed by homozygosity of the major G allele. No association was found between the remaining three evaluated SNPs and CAD. Nevertheless, the study suggests that the IL4R Cys688 variant reduces the risk of CAD in miniature dachshunds.
ISSN:0916-7250
1347-7439
DOI:10.1292/jvms.20-0301