Angiotensinogen gene G-6A polymorphism influences idiopathic pulmonary fibrosis disease progression.
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.
Servicio de Neumología, Hospital Clínic, Instituto de Investigaciones Biomédicas Agusti Pi Suñer, Barcelona, Spain. mariamolinamolina@hotmail.com
M
M
Molina-Molina
A
A
Xaubet
X
X
Li
A
A
Abdul-Hafez
K
K
Friderici
K
K
Jernigan
W
W
Fu
Q
Q
Ding
J
J
Pereda
A
A
Serrano-Mollar
A
A
Casanova
E
E
Rodríguez-Becerra
F
F
Morell
J
J
Ancochea
C
C
Picado
B D
BD
Uhal
D000328:Adult; D000368:Aged; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006147:Guanine / Q000737:chemistry; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011659:Pulmonary Gas Exchange
D000808:Angiotensinogen; D006147:Guanine