- 著者
-
Ito Michiko
Hanaoka Masayuki
Droma Yunden
Hatayama Orie
Sato Etsuro
Katsuyama Yoshihiko
Fujimoto Keisaku
Ota Masao
- 出版者
- The Japanese Society of Internal Medicine
- 雑誌
- Internal Medicine (ISSN:09182918)
- 巻号頁・発行日
- vol.47, no.15, pp.1387-1394, 2008
- 被引用文献数
-
1
29
<b>Objective</b> The transforming growth factor beta-1 gene (<i>TGFB1</i>) is one of the most promising candidate genes for chronic obstructive pulmonary disease (COPD). Several case-control studies have been performed and generated inconsistent results. The possible reasons for these discrepancies include the diversity of ethnic populations and the heterogeneity of COPD, including emphysema and airway disease. We designed this study to investigate the association of single nucleotide polymorphisms (SNPs) of <i>TGFB1</i> with the emphysema phenotype in the Japanese population.<br> <b>Methods</b> Eight SNPs in <i>TGFB1</i> (<i>rs2241712</i>, <i>rs1982072</i>, and <i>rs1800469</i> in the promoter region; <i>rs1982073</i> in exon 1; <i>rs2241716</i> and <i>rs4803455</i> in intron 2; <i>rs6957</i> and <i>rs2241718</i> in the 3' region) were genotyped by allelic discrimination assays in 70 COPD patients with emphysema phenotype and 99 healthy smokers. The emphysema phenotype was identified by high-resolution computed tomography imaging using Goddard's method.<br> <b>Results</b> The frequency of one significant haplotype structured by the eight SNPs was significantly higher in the emphysema group (10%) than in the healthy smokers (4%, p=0.02). In the emphysema group, the predicted value of forced expiratory volume in 1 second after bronchodilator administration was significantly associated with the minor alleles of the two SNPs (<i>rs1800469</i> and <i>rs1982073</i>, p=0.007 and 0.032, respectively), however, the low attenuation area and carbon monoxide diffusing capacity were not associated with the SNPs. In addition, the <i>rs1800469T</i> and <i>rs1982073C</i> alleles were significantly more prevalent in patients with severe and very severe airflow limitation than in those with mild and moderate airflow limitation (p=0.007 and 0.041, respectively).<br> <b>Conclusions</b> One significant haplotype of <i>TGFB1</i> is associated with the emphysema phenotype in the Japanese population. Two <i>TGFB1</i> SNPs (<i>rs1800469</i> and <i>rs1982073</i>) are associated with the severity of COPD in patients with emphysema phenotype.<br>