Variations in the C3, C3a receptor, and C5 genes affect susceptibility to bronchial asthma
Variations in the C3, C3a receptor, and C5 genes affect susceptibility to bronchial asthma
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DOI：
10.1007/s00439-004-1157-z
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发表时间：
2004-09-01
期刊：
影响因子：
5.3
通讯作者：
Suzuki, Y
中科院分区：
文献类型：
--
作者：
Hasegawa, K;Tamari, M;Suzuki, Y
支气管哮喘（BA）是一种常见的慢性炎症性疾病，其特征是气道反应性增强、粘液产生过多、嗜酸性粒细胞活化和IgE产生。补体系统在先天性和获得性免疫的界面处起免疫调节作用。最近的研究提供了证据，C3，C3 a受体，和C5与气道高反应性。为了确定补体系统基因的遗传变异是否会影响对BA的易感性，我们筛选了C3、C5、C3 a受体基因（C3 AR 1）和C5 a受体基因（C5 R1）的单核苷酸多态性（SNP），并在日本人群中进行了关联研究。该SNP病例对照研究的结果表明C3基因中的4896 C/T与特应性儿童BA（P=0.0078）以及成人BA（P=0.010）之间存在关联。当根据总IgE水平升高对患者数据进行分层时，4896 C/T与成人BA更密切相关（P=0.0016）。仅患者相关研究表明，儿童BA的严重程度与C3 AR 1基因的1526 G/A相关（P=0.0057）。我们确定了儿童（P=0.0021）和成人BA（P=0.0058）的C3基因的高风险单倍型和成人BA的低风险单倍型（P=0.00011）。我们还鉴定了C5基因的单倍型，其对儿童BA（P=1.4x10（-6））和成人BA（P=0.00063）具有保护作用。这些结果表明，补体系统的C3和C5途径在BA的发病机制中起重要作用，这些基因的多态性影响BA的易感性。
Bronchial asthma (BA) is a common chronic inflammatory disease characterized by hyperresponsive airways, excess mucus production, eosinophil activation, and the production of IgE. The complement system plays an immunoregulatory role at the interface of innate and acquired immunities. Recent studies have provided evidence that C3, C3a receptor, and C5 are linked to airway hyperresponsiveness. To determine whether genetic variations in the genes of the complement system affect susceptibility to BA, we screened single nucleotide polymorphisms (SNPs) in C3, C5, the C3a receptor gene (C3AR1), and the C5a receptor gene (C5R1) and performed association studies in the Japanese population. The results of this SNP case-control study suggested an association between 4896C/T in the C3 gene and atopic childhood BA (P=0.0078) as well as adult BA (P=0.010). When patient data were stratified according to elevated total IgE levels, 4896C/T was more closely associated with adult BA (P=0.0016). A patient-only association study suggested that severity of childhood BA was associated with 1526G/A of the C3AR1 gene (P=0.0057). We identified a high-risk haplotype of the C3 gene for childhood (P=0.0021) and adult BA (P=0.0058) and a low-risk haplotype for adult BA (P=0.00011). We also identified a haplotype of the C5 gene that was protective against childhood BA (P=1.4x10(-6)) and adult BA (P=0.00063). These results suggest that the C3 and C5 pathways of the complement system play important roles in the pathogenesis of BA and that polymorphisms of these genes affect susceptibility to BA.