Angiotensin-Converting Enzyme (ACE) Gene Polymorphisms are Associated with Idiopathic Pulmonary Fibrosis
- 381 Downloads
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.
KeywordsAngiotensin-converting enzyme Genetic polymorphism Genotype Pulmonary fibrosis SNPs
The DNA samples were generously provided by the Soonchunhyang University, Bucheon Hospital Biobank, a member of the National Biobank of Korea, supported by the Ministry of Health, Welfare and Family Affairs, Republic of Korea (Approval No. SCHBC-IRB-06-05). The English in this manuscript has been checked by textcheck (www.textcheck.com/certificate/RfXz47).
Conflict of interest
The authors declare that they have no conflicts of interest.
- 1.American Thoracic Society/European Respiratory Society (2002) American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 165:277–304CrossRefGoogle Scholar
- 10.Mushiroda T, Wattanapokayakit S, Takahashi A, Nukiwa T, Kudoh S, Ogura T, Taniguchi H, Kubo M, Kamatani N, Nakamura Y (2008) A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. J Med Genet 45:654–656PubMedCrossRefGoogle Scholar
- 16.Travis WD, Matsui K, Moss J, Ferrans VJ (2000) Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns: survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia. Am J Surg Pathol 24:19–33PubMedCrossRefGoogle Scholar
- 19.Villard E, Tiret L, Visvikis S, Rakotovao R, Cambien F, Soubrier F (1996) Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis. Am J Hum Genet 58:1268–1278PubMedGoogle Scholar
- 21.Stephens JC, Schneider JA, Tanguay DA, Choi J, Acharya T, Stanley SE, Jiang R, Messer CJ, Chew A, Han JH, Duan J, Carr JL, Lee MS, Koshy B, Kumar AM, Zhang G, Newell WR, Windemuth A, Xu C, Kalbfleisch TS, Shaner SL, Arnold K, Schulz V, Drysdale CM, Nandabalan K, Judson RS, Ruano G, Vovis GF (2001) Haplotype variation and linkage disequilibrium in 313 human genes. Science 293:489–493PubMedCrossRefGoogle Scholar