Genetic Impact of a Butyrophilin-like 2 (BTNL2) Gene Variation on Specific IgE Responsiveness to Dermatophagoides farinae (Der f) in Japanese
Genetic Impact of a Butyrophilin-like 2 (BTNL2) Gene Variation on Specific IgE Responsiveness to Dermatophagoides farinae (Der f) in Japanese
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DOI：
10.2332/allergolint.08-oa-0005
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发表时间：
2009-03-01
影响因子：
6.8
通讯作者：
Nishimura, Masaharu
中科院分区：
文献类型：
--
作者：
Konno, Satoshi;Takahashi, Daisuke;Nishimura, Masaharu
粉尘螨（Dermatophagoides farinae，Der f）是多种过敏性疾病中最常见的过敏原之一。几个全基因组筛选已经确定了染色体6p 21和螨特异性IgE反应性之间的联系。嗜酪蛋白样2（BTNL 2）是免疫球蛋白超家族的成员，并且基于其与B7-1的同源性，被认为是参与T细胞活化的共刺激分子。BTNL 2位于染色体6p 21的HLA区域，BTNL 2基因多态性与多种炎症性疾病有显著相关性。目的：探讨BTNL 2基因多态性与Der f特异性IgE反应的关系。编码SNP之一是rs 2076530 A > G，其具有功能性后果。共有863名无关的日本受试者（447例IgE阳性和416例IgE阴性）被招募进行病例对照研究。控制性别、年龄、吸烟和哮喘的存在，多元逻辑回归分析显示rs 2076530 A等位基因的纯合性，已报道为结节病的危险等位基因，与对Der f致敏的风险相关（比值比; 1.55，p = 0.0060）。尽管需要排除可能由于与6p 21中其他基因的连锁不平衡而导致的关联，本研究结果提示BTNL 2基因可能是导致Derf特异性IgE反应性发病的候选基因之一。
Background: Dermatophagoides farinae (Der f) is one of the most frequently implicated allergens in several allergic diseases. Several genome-wide screens have identified a linkage between chromosome 6p21 and mite-specific IgE responsiveness. Butyrophilin-like 2 (BTNL2) is a member of the immunoglobulin superfamily and, on the basis of its homology to B7-1, has been implicated as a costimulatory molecule involved in T-cell activation. BTNL2 resides in the HLA region on chromosome 6p21, and significant associations between BTNL2 gene polymorphisms and several inflammatory diseases have been reported.Objective: The aim of this study was to examine whether BTNL2 gene polymorphisms are associated with specific IgE responses to Der f.Methods: Three single nucleotide polymorphisms (SNIPS), including 2 coding SNPs and 1 intron SNP, were studied. One of the coding SNPs was the rs2076530 A > G, which has a functional consequence. A total of 863 unrelated Japanese subjects (447 positive and 416 negative for IgE to Der f) were recruited for a case-control study.Results: Controlling for gender, age, smoking, and the presence of asthma, multiple logistic regression analyses showed that homozygosity of the rs2076530 A allele, which has been reported to be a risk allele for sarcoidosis, was associated with a risk of sensitization towards Der f (Odds ratio; 1.55, p = 0.0060).Conclusions: Although an association which may be due to the linkage disequilibrium with other genes in 6p 21 needs to be ruled out, the present findings suggest that the BTNL2 gene might be one of the candidate genes that is responsible for the pathogenesis of Der f-specific IgE responsiveness.