Division of Allergy and Respiratory Medicine, Soonchunhyang University Seoul Hospital, 657, Hannam-dong, Yongsan-gu, Seoul, 140-743, South Korea.
Lung. 2013 Aug;191(4):345-51. doi: 10.1007/s00408-013-9469-1. Epub 2013 May 9.
Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea and worsening lung function. ACE is increased in the bronchoalveolar lavage fluid from patients with IPF, suggesting the role of ACE in the pathogenesis of IPF. We evaluated the role of single-nucleotide polymorphisms (SNPs) in the development risk of IPF.
Two-hundred twenty patients with IPF and 456 healthy subjects were included in this study. Eleven polymorphisms were selected among those reported previously. Genotype was performed by single base extension.
Although absolute LD (|D'|= 1 and r(2 )= 1) was not present, 11 SNPs showed tight LDs. The logistic analysis of the all of 11 SNPs on the ACE genes between patients with IPF and healthy subjects were found to be related with the risk of IPF in recessive type. However, in patients with IPF diagnosed by surgical lung biopsy, only two SNP of -5538T>C and +21288_insdel SNPs were related with the risk of IPF in co-dominant type, and there were no SNPs related with the risk of IPF in dominant type. In patients with IPF diagnosed by clinical criteria or surgical lung biopsy, four SNPs on promoter (-5538T>C, -5508A>C, -3927T>C, -115T>C), one on intron (+15276A>G), one on exon (+21181G>A), and one in three prime region (+21288_insdel) were related with the risk of IPF.
This study showed a newly discovered SNP of ACE associated with the risk of development of IPF. ACE -5538T>C and -5508A>C significantly associated with risk of IPF in Korea.
特发性肺纤维化（IPF）的特征是进行性呼吸困难和肺功能恶化。ACE 在 IPF 患者的支气管肺泡灌洗液中增加，表明 ACE 在 IPF 的发病机制中起作用。我们评估了单核苷酸多态性（SNP）在 IPF 发病风险中的作用。
本研究纳入 220 例 IPF 患者和 456 例健康对照者。选择了先前报道的 11 种多态性。通过单碱基延伸进行基因型分析。
虽然绝对 LD（|D'|=1 和 r(2)=1）不存在，但 11 个 SNP 显示出紧密的 LD。对 IPF 患者和健康对照组 ACE 基因中所有 11 个 SNP 的逻辑分析发现，在隐性类型中与 IPF 的发病风险有关。然而，在通过外科肺活检诊断的 IPF 患者中，仅 -5538T>C 和 +21288_insdel 两个 SNP 与 IPF 的发病风险呈共显性相关，而显性类型中没有与 IPF 发病风险相关的 SNP。在通过临床标准或外科肺活检诊断的 IPF 患者中，启动子上的 4 个 SNP（-5538T>C、-5508A>C、-3927T>C、-115T>C）、1 个内含子上的 SNP（+15276A>G）、1 个外显子上的 SNP（+21181G>A）和 1 个 3 端区域的 SNP（+21288_insdel）与 IPF 的发病风险相关。
本研究发现了一个与 ACE 相关的新 SNP，与 IPF 的发病风险有关。ACE-5538T>C 和 -5508A>C 与韩国的 IPF 风险显著相关。
