Variation in IL7R predisposes to sarcoid inflammation
Variation in IL7R predisposes to sarcoid inflammation
复制标题
DOI：
10.1038/gene.2009.55
复制
发表时间：
2009-10-01
影响因子：
5
通讯作者：
van den Bosch, J. M. M.
中科院分区：
文献类型：
--
作者：
Heron, M.;Grutters, J. C.;van den Bosch, J. M. M.
结节病是一种慢性肉芽肿性疾病，其特征是大量Th 1淋巴细胞流入。初始和记忆T细胞都表达高水平的白细胞介素7受体-α（IL 7 R α），由IL 7 R基因编码。本研究的目的是探讨IL 7 R基因区域在结节病易感性中的作用。我们对475例结节病患者和465例健康对照者的6个常见单核苷酸多态性（SNPs）进行了基因分型和分析。在206名独立的结节病患者、127名对照和126名洛夫格伦病患者中复制一个显著相关的SNP。rs 10213865单核苷酸多态性与结节病相关（P = 0.008），计算机模拟分析显示与外显子6的功能性非同义编码单核苷酸多态性（rs6897932，T244 I）完全连锁（r（2）= 1，D' = 1）。对663名结节病患者和586名对照者（风险等位基因纯合子携带者，P = 5 × 10（-4），比值比1.49（1.19-1.86））的联合分析为IL 7 R与结节病风险的真正关联提供了强有力的统计学支持。此外，我们报告了IL-7 R基因变异与洛夫格伦病患者之间的相同趋势，表明IL-7 R变异可能会导致肉芽肿性肺病的发生。Genes and Immunity（2009）10，647-653; doi：10.1038/gene.2009.55; 2009年7月23日在线发表
Sarcoidosis is a chronic granulomatous disorder characterized by a massive influx of Th1 lymphocytes. Both naive and memory T cells express high levels of interleukin 7 receptor-alpha (IL7R alpha), encoded by the IL7R gene. The purpose of this study was to investigate the role of the IL7R gene region in susceptibility to sarcoidosis. Six common single-nucleotide polymorphisms (SNPs) spanning IL7R were genotyped and analyzed in 475 sarcoidosis patients and 465 healthy controls. Replication of one significant associated SNP was carried out in 206 independent sarcoidosis patients, 127 controls and 126 patients with Lofgren's disease. The rs10213865 SNP was associated with sarcoidosis (P = 0.008), and in silico analysis showed a complete linkage (r(2) = 1, D' = 1) with a functional nonsynonymous coding SNP in exon 6 (rs6897932, T244I). Combined analysis of 663 individuals with sarcoidosis and 586 controls (homozygous carriers of risk allele, P = 5 x 10(-4), odds ratio 1.49 (1.19-1.86)) provided strong statistical support for a genuine association of IL7R with the risk of sarcoidosis. In addition, we report the same trend between variation in the IL7R gene and patients with Lofgren's disease, suggesting that variation in IL7R may confer general risk for developing granulomatous lung disease. Genes and Immunity (2009) 10, 647-653; doi:10.1038/gene.2009.55; published online 23 July 2009