Mai H N, Hijikata M, Inoue Y, Suzuki K, Sakatani M, Okada M, Kimura K, Kobayashi N, Toyota E, Kudo K, Nagai H, Kurashima A, Kajiki A, Oketani N, Hayakawa H, Tanaka G, Shojima J, Matsushita I, Sakurada S, Tokunaga K, Keicho N
Department of Respiratory Diseases, Research Institute, International Medical Centre of Japan, Tokyo, Japan.
Int J Tuberc Lung Dis. 2007 Jul;11(7):808-13.
The T5 allele in intron 8 (IVS8) on specific haplotype backgrounds (e.g., long TG repeats) causes abnormal splicing in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and is also known to be associated with chronic airway diseases.
To investigate the role of CFTR variations for susceptibility to pulmonary Mycobacterium avium complex (MAC) infection.
Three hundred patients with pulmonary MAC infection (72 males, 228 females; mean age at onset 61.6 + or - 12.4 years) took part in this study. Diagnosis of MAC infection was based on American Thoracic Society criteria. Clinical profiles were collected and blood samples were genotyped for TG repeats, poly-T and M470V polymorphisms.
We found significantly higher T5 frequency in MAC patients than in healthy controls from our own study (0.035 and 0.005, respectively, P = 0.023) and other reports. Homozygote for the T5 allele was found in two MAC patients. All T5 alleles were associated with longer TG repeats, the TG12 or TG13 allele. Seventeen of the 21 T5 alleles appeared to be associated with the V470 allele. Other polymorphisms did not show any significant differences in frequency.
These findings suggest that the IVS8 5T allele might be involved in susceptibility to pulmonary MAC infection.
特定单倍型背景（如长TG重复序列）下内含子8（IVS8）中的T5等位基因会导致囊性纤维化跨膜传导调节因子（CFTR）基因异常剪接，并且已知其与慢性气道疾病相关。
研究CFTR变异在肺部鸟分枝杆菌复合群（MAC）感染易感性中的作用。
300例肺部MAC感染患者（男性72例，女性228例；发病时平均年龄61.6±12.4岁）参与了本研究。MAC感染的诊断基于美国胸科学会标准。收集临床资料并对血样进行TG重复序列、多聚T和M470V多态性基因分型。
我们发现MAC患者中T5频率显著高于我们自己研究中的健康对照（分别为0.035和0.005，P = 0.023）以及其他报告中的数据。在两名MAC患者中发现了T5等位基因纯合子。所有T5等位基因均与更长的TG重复序列相关，即TG12或TG13等位基因。21个T5等位基因中有17个似乎与V470等位基因相关。其他多态性在频率上未显示出任何显著差异。
这些发现表明IVS8 5T等位基因可能参与肺部MAC感染的易感性。
