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首页> 外文期刊>Tissue antigens. >Association of canine anal furunculosis with TNFA is secondary to linkage disequilibrium with DLA-DRB1*.
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Association of canine anal furunculosis with TNFA is secondary to linkage disequilibrium with DLA-DRB1*.

机译：犬肛门呋喃菌病与TNFA的关联是继与DLA-DRB1 *连锁不平衡之后的结果。

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摘要

Anal furunculosis (AF) is a chronic inflammatory disease of perianal tissues that particularly affects German Shepherd dogs (GSD). An immune-mediated aetiopathogenesis is suggested by T-cell infiltration, upregulated cytokine gene expression, clinical response to ciclosporin therapy and a strong genetic association with the DLA-DRB1*00101 allele. Given the close proximity of TNFA and DLA-DRB1 in the canine major histocompatibility complex (MHC), together with the strong linkage disequilibrium (LD) observed across this region, the primary disease association could be with either locus. We have investigated whether there may be an association of AF with TNFA gene polymorphism in GSDs. Cohorts of AF-affected and AF-unaffected GSDs of known dog leucocyte antigen (DLA) class II profile were genotyped for 10 single nucleotide polymorphisms (SNPs) in the canine TNFA locus using Sequenom iPLEX technology. Seven discrete TNFA haplotypes were identified in GSDs for combinations of these SNPs. TNFA haplotype frequencies were compared in cases and controls. The TNFA haplotype 3 (ATCGTTACGG), was at significantly increased frequency in cases (29% vs 15%, OR 2.5, 95% CI 1.4-4.8; P = 0.003). All seven discrete TNFA SNP haplotypes were examined for their association with DLA-DRB1/DQA1/DQB1 established haplotypes. TNFA haplotype 3 was preferentially associated with both DLA-DRB1*00101(3A)- and DLA-DRB1*00102(3B)-positive haplotypes. The DLA-DRB1* 00101/TNFA-3A haplotype was significantly associated with AF (19.3% vs 5.8%; OR 3.7, 95% CI: 1.5-8.9; P = 0.003), whereas the DLA-DRB1*00102/TNFA-3B haplotype was not (P = NS). These findings suggest that susceptibility to AF in GSDs is primarily associated with DLA-DRB1*00101 and any association with the TNFA locus is secondary and is likely to be because of LD.
机译：肛门真菌病（AF）是一种肛周组织的慢性炎性疾病，特别影响德国牧羊犬（GSD）。 T细胞浸润，细胞因子基因表达上调，对环孢菌素治疗的临床反应以及与DLA-DRB1 * 00101等位基因的强遗传关联提示了免疫介导的发病机理。鉴于犬主要组织相容性复合体（MHC）中的TNFA和DLA-DRB1紧密相邻，并且在该区域观察到的强烈连锁不平衡（LD），原发疾病可能与任一基因位点有关。我们研究了在GSD中是否可能将AF与TNFA基因多态性联系起来。使用Sequenom iPLEX技术，对犬TNFA基因座中10个单核苷酸多态性（SNP）进行基因分型，对已知狗白细胞抗原（DLA）II类谱的AF影响和AF影响的GSD进行基因分型。在GSD中，针对这些SNP的组合鉴定出7种离散的TNFA单倍型。比较了病例和对照组的TNFA单倍型频率。在某些情况下，TNFA单倍型3（ATCGTTACGG）的发生频率显着增加（29％比15％，OR 2.5，95％CI 1.4-4.8; P = 0.003）。检查所有七个离散的TNFA SNP单倍型与DLA-DRB1 / DQA1 / DQB1建立的单倍型的关联。 TNFA单倍型3优先与DLA-DRB1 * 00101（3A）-和DLA-DRB1 * 00102（3B）阳性单倍型相关。 DLA-DRB1 * 00101 / TNFA-3A单倍型与AF显着相关（19.3％vs 5.8％; 3.7，95％CI：1.5-8.9; P = 0.003），而DLA-DRB1 * 00102 / TNFA-3B单倍型不是（P = NS）。这些发现表明，GSD中对AF的敏感性主要与DLA-DRB1 * 00101相关，与TNFA基因座的任何相关性都是继发性的，很可能是由于LD引起的。

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