The association of transforming growth factor beta 1 gene polymorphisms with the emphysema phenotype of COPD in Japanese
The association of transforming growth factor beta 1 gene polymorphisms with the emphysema phenotype of COPD in Japanese
复制标题
DOI：
10.2169/internalmedicine.47.1116
复制
发表时间：
2008-01-01
影响因子：
1.2
通讯作者：
Ota, Masao
中科院分区：
文献类型：
--
作者：
Ito, Michiko;Hanaoka, Masayuki;Ota, Masao
目的 转化生长因子β1基因（TGFB1）是慢性阻塞性肺疾病（COPD）最有希望的候选基因之一。已经进行了几项病例对照研究，但得出的结果不一致。造成这些差异的可能原因包括种族人口的多样性和慢性阻塞性肺病（包括肺气肿和气道疾病）的异质性。我们设计本研究的目的是调查 TGFB1 的单核苷酸多态性 (SNP) 与日本人群肺气肿表型的关联。 方法 TGFB1 中的 8 个 SNP（启动子区域的 rs2241712、rs1982072 和 rs1800469；外显子 1 的 rs1982073；外显子 1 的 rs2241716 和通过等位基因区分分析对 70 名患有肺气肿表型的 COPD 患者和 99 名健康吸烟者进行基因分型。采用Goddard方法通过高分辨率计算机断层扫描成像来鉴定肺气肿表型。结果由8个SNP构成的一种显着单倍型的频率在肺气肿组中(10%)显着高于健康吸烟者(4%，p=0.02)。在肺气肿组中，给予支气管扩张剂后1秒用力呼气量的预测值与两个SNP（rs1800469和rs1982073，分别p=0.007和0.032）的次要等位基因显着相关，然而，低衰减面积和一氧化碳扩散能力与SNP无关。此外，rs1800469T和rs1982073C等位基因在重度和极重度气流受限的患者中比在轻度和中度气流受限的患者中显着更常见（分别为p=0.007和0.041）。 结论 TGFB1的一个显着单倍型与日本人群中的肺气肿表型相关。两个 TGFB1 SNP（rs1800469 和 rs1982073）与肺气肿表型患者 COPD 的严重程度相关。
Objective The transforming growth factor beta-1 gene (TGFB1) 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 TGFB1 with the emphysema phenotype in the Japanese population.Methods Eight SNPs in TGFB1 (rs2241712, rs1982072, and rs1800469 in the promoter region; rs1982073 in exon 1; rs2241716 and rs4803455 in intron 2; rs6957 and rs2241718 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.Results 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 (rs1800469 and rs1982073, 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 rs1800469T and rs1982073C 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).Conclusions One significant haplotype of TGFB1 is associated with the emphysema phenotype in the Japanese population. Two TGFB1 SNPs (rs1800469 and rs1982073) are associated with the severity of COPD in patients with emphysema phenotype.