Journal
EUROPEAN RESPIRATORY JOURNAL
Volume 32, Issue 4, Pages 1004-1008Publisher
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00015808
Keywords
angiotensin system; genetics; interstitial lung disease
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Funding
- NHLBI NIH HHS [R01 HL045136-21] Funding Source: Medline
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Angiotensin II is a growth factor that plays a key role in the physiopathology of idiopathic pulmonary fibrosis (IPF). A nucleotide substitution of an adenine instead of a guanine (G-6A) in the proximal promoter region of angiotensinogen (AGT), the precursor of angiotensin II, has been associated with an increased gene transcription rate. In order to investigate whether the G-6A polymorphism of the AGT gene is associated with IPF development, severity and progression, the present study utilised a case-control study design and genotyped G-6A in 219 patients with IPF and 224 control subjects. The distribution of G-6A genotypes and alleles did not significantly differ between cases and controls. The G-6A polymorphism of the AGT gene was not associated with disease severity at diagnosis. The presence of the A allele was strongly associated with increased alveolar arterial oxygen tension difference during follow-up, after controlling for the confounding factors. Higher alveolar arterial oxygen tension changes over time were observed in patients with the AA genotype (0.37 +/- 0.7 mmHg (0.049 +/- 0.093 kPa) per month) compared to GA genotype (0.12 +/- 1 mmHg (0.016 +/- 0.133 kPa) per month) and GG genotype (0.2 +/- 0.6 mmHg (0.027 +/- 0.080 kPa) per month). G-6A polymorphism of the angiotensinogen gene is associated with idiopathic pulmonary fibrosis progression but not with disease predisposition. This polymorphism could have a predictive significance in idiopathic pulmonary fibrosis patients.
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