Angiotensinogen gene G-6A polymorphism influences Idiopathic Pulmonary Fibrosis disease progression

¹ Servicio de Neumología, Hospital Clínico, Barcelona, Spain. IDIBAPS; and Centro Investigaciones Biomédicas en Red (CIBER) de Enfermedades Respiratorias
² Dept of Physiology
³ Dept of Microbiology and Molecular Genetics
⁴ Dept of Epidemiology Michigan State University. East Lansing. Michigan. US
⁵ Dept de Patología Experimental, IIBB, CSIC, Barcelona; and Centro Investigaciones Biomédicas en Red (CIBER) de Enfermedades Respiratorias
⁶ Servicio de Neumología Hospital La Princesa, Madrid. Spain
⁷ Servicio de Neumología, Hospital Virgen del Rocio, Sevilla
⁸ Servicio de Neumología. Hospital Vall d’Hebron, Barcelona; and Centro Investigaciones Biomédicas en Red (CIBER) de Enfermedades Respiratorias

^* To whom correspondence should be addressed. E-mail: mariamolinamolina{at}hotmail.com.

	Abstract

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 increased gene transcription rate.

To investigate whether the G-6A polymorphism of the AGT gene is associated with IPF development, severity and progression.

We used a case-control design study 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. G-6A polymorphism of AGT gene was not associated with disease severity at diagnosis. The presence of A allele was strongly associated with increased alveolar arterial oxygen tension difference during follow-up (p=0.001), after controlling for the confounding factors. Higher alveolar arterial oxygen tension changes over time were observed in patients with AA genotype (0.37±0.7 mmHg·month^-1) compared to GA genotype (0.12±1 mmHg·month^-1, p=0.0015) and GG genotype (0.2±0.6 mmHg·month^-1, p=0.005).

G-6A polymorphism of the AGT gene is associated with IPF progression but not with disease predisposition. This polymorphism could have a predictive significance in IPF patients.

This article has been cited by other articles:

				A. Abdul-Hafez, R. Shu, and B. D. Uhal JunD and HIF-1{alpha} mediate transcriptional activation of angiotensinogen by TGF-{beta}1 in human lung fibroblasts FASEB J, June 1, 2009; 23(6): 1655 - 1662. [Abstract] [Full Text] [PDF]

				J. P. Lynch III Idiopathic Pulmonary Fibrosis, Nonspecific Interstitial Pneumonia/Fibrosis, and Sarcoidosis ACCP Pulmonary Med Brd Rev, January 1, 2009; 25(0): 635 - 686. [Full Text] [PDF]