Mercier Elise, Peters Iain R, Farnir Frédéric, Lavoué Rachel, Day Michael, Clercx Cécile, Peeters Dominique
BMC Vet Res. 2014 Aug 16;10:187. doi: 10.1186/s12917-014-0187-6.
The exact aetiology of canine sino-nasal aspergillosis (SNA) is unknown. In man, dysfunction in innate immunity, particularly in the function of pattern recognition receptors, is implicated in the pathogenesis of inflammatory sino-nasal disease and in fungal diseases. Associations between single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and these diseases have been identified. Similarly, in dogs SNPs in genes encoding TLRs may be important in the pathogenesis of SNA. The aims of the present study were (1) to identify the presence of non-synonymous SNPs in the coding regions of the TLR2, 4 and 9 genes in dogs suffering from SNA, and (2) to investigate the SNP genotypes in dogs with SNA compared with a control population.
Direct sequencing of nine dogs of various breeds with SNA revealed two non-synonymous SNPs in the coding region of TLR2, eight in TLR4 and four in TLR9. These non-synonymous SNPs were further evaluated in a case-control study of affected Golden Retrievers, Labrador Retrievers, Rottweilers and Beaucerons. Genotyping was performed using a combination of allele-specific primers and hydrolysis probe assays in 31 dogs with SNA and 31 controls. No significant difference in minor allele frequency was identified between these groups, for all studied SNPs, in any of the four breeds.
These findings do not support a role for non-synonymous SNPs in the TLR 2, 4 and 9 coding regions in the pathogenesis of canine SNA, but do not exclude a role for innate immunity in the pathogenesis of the disease.
犬鼻窦曲霉菌病(SNA)的确切病因尚不清楚。在人类中,先天免疫功能障碍,特别是模式识别受体的功能,与炎症性鼻窦疾病和真菌疾病的发病机制有关。已确定Toll样受体(TLR)中的单核苷酸多态性(SNP)与这些疾病之间的关联。同样,在犬类中,编码TLR的基因中的SNP可能在SNA的发病机制中起重要作用。本研究的目的是:(1)确定患有SNA的犬类中TLR2、4和9基因编码区非同义SNP的存在情况,以及(2)将患有SNA的犬类与对照群体的SNP基因型进行比较。
对9只患有SNA的不同品种犬进行直接测序,发现在TLR2编码区有2个非同义SNP,TLR4中有8个,TLR9中有4个。在一项对受影响的金毛寻回犬、拉布拉多寻回犬、罗威纳犬和博瑞犬的病例对照研究中,对这些非同义SNP进行了进一步评估。使用等位基因特异性引物和水解探针分析相结合的方法,对31只患有SNA的犬和31只对照犬进行基因分型。在四个品种中的任何一个品种中,所有研究的SNP在这些组之间的次要等位基因频率均未发现显著差异。
这些发现不支持TLR 2、4和9编码区的非同义SNP在犬SNA发病机制中起作用,但不排除先天免疫在该疾病发病机制中的作用。