Positional identification of an asthma susceptibility gene on human chromosome 5q33.
Positional identification of an asthma susceptibility gene on human chromosome 5q33.
复制标题
DOI：
10.1164/rccm.200409-1223oc
复制
发表时间：
2005-07
影响因子：
24.7
通讯作者：
E. Noguchi;Y. Yokouchi;Jiang Zhang;K. Shibuya;A. Shibuya;M. Bannai;K. Tokunaga;Hitomi Doi;M. Tamari;M. Shimizu;T. Shirakawa;M. Shibasaki;K. Ichikawa;T. Arinami
中科院分区：
文献类型：
--
作者：
E. Noguchi;Y. Yokouchi;Jiang Zhang;K. Shibuya;A. Shibuya;M. Bannai;K. Tokunaga;Hitomi Doi;M. Tamari;M. Shimizu;T. Shirakawa;M. Shibasaki;K. Ichikawa;T. Arinami
哮喘是一种常见的呼吸系统疾病，具有复杂的遗传成分。我们之前报道了螨虫敏感性哮喘与染色体5q33标记之间联系的有力证据。这个连锁区域包括一个与小鼠区域同源的区域，该区域包含一个参与气道高反应性调节的位点。目的鉴定5q33染色体上的哮喘易感基因。方法与结果我们对9.4 mb人类连锁区基因进行了突变筛选和关联分析。对155个哮喘家族105个多态性的遗传不平衡检验分析显示，细胞质脆性X智力迟钝蛋白（FMRP）相互作用蛋白2基因的6个多态性与哮喘的发生有显著相关性（p = 0.000075，优势比为5.9）。这6个多态性处于完全连锁不平衡状态。在实时定量聚合酶链反应分析中，纯合子过遗传给哮喘后代的受试者淋巴细胞中FMRP相互作用蛋白2基因表达水平显著高于杂合子的受试者（p = 0.038）。结论：我们的数据表明，胞质FMRP相互作用蛋白2与人类特应性哮喘的发展有关，靶向胞质FMRP相互作用蛋白2可能是治疗特应性哮喘的一种新策略。
RATIONALE Asthma is a common respiratory disease with complex genetic components. We previously reported strong evidence for linkage between mite-sensitive asthma and markers on chromosome 5q33. This area of linkage includes a region homologous to a mouse area that contains a locus involved in regulation of airway hyperreactivity. OBJECTIVE The aim of the present study is to identify asthma susceptibility genes on chromosome 5q33. METHODS AND RESULTS We performed mutation screening and association analyses of genes in the 9.4-Mb human linkage region. Transmission disequilibrium test analysis of 105 polymorphisms in 155 families with asthma revealed that six polymorphisms in cytoplasmic fragile X mental retardation protein (FMRP)-interacting protein 2 gene were associated significantly with the development of asthma (p = 0.000075; odds ratio, 5.9). These six polymorphisms were in complete linkage disequilibrium. In real-time quantitative polymerase chain reaction analysis, subjects homozygous for the haplotype overtransmitted to asthma-affected offspring showed significantly increased level of cytoplasmic FMRP interacting protein 2 gene expression in lymphocytes compared with ones heterozygous for the haplotype (p = 0.038). CONCLUSIONS Our data suggest that cytoplasmic FMRP interacting protein 2 are associated with the development of atopic asthma in humans, and that targeting cytoplasmic FMRP interacting protein 2 could be a novel strategy for treating atopic asthma.