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Erschienen in:

01.08.2013

Angiotensinogen Promoter Polymorphisms Predict Low Diffusing Capacity in U.S. and Spanish IPF Cohorts

verfasst von: My-Trang T. Dang, Chenyang Gu, Jeannie I. Klavanian, Katherine A. Jernigan, Karen H. Friderici, Yuehua Cui, Maria Molina-Molina, Julio Ancochea, Antoni Xaubet, Bruce D. Uhal

Erschienen in: Lung | Ausgabe 4/2013

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Abstract

Background

Single nucleotide polymorphisms (SNPs) in angiotensinogen (AGT) at positions −20 and −6 are associated with increased severity and progression of various fibrotic diseases. Our earlier work demonstrated that the progression of idiopathic pulmonary fibrosis (IPF) was associated with the A-6 allele. This study examined the hypothesis that the homozygous CC genotype at −20 and the AA genotype at −6 would confer worse measures of pulmonary function (measured by pulmonary function tests) in IPF.

Methods

Multiple logistic regression analysis was applied to a NIH Lung Tissue Research Consortium cohort and a Spanish cohort, while also adjusting for covariates to determine the effects of these SNPs on measures of pulmonary function.

Results

Analysis demonstrated that the CC genotype at −20 was strongly associated with reduced diffusing capacity in males in both cohorts (p = 0.0028 for LTRC and p = 0.017 for the Spanish cohort). In females, the AA genotype was significantly associated with lower FVC (p = 0.0082) and V _alv (p = 0.022). In males, the haplotype CA at −20 and −6 in AGT was also strongly associated with reduced diffusing capacity in both cohorts.

Conclusions

This study is the first to demonstrate an association of AGT polymorphisms (−20A > C and −6G > A) with lower measures of pulmonary function in IPF. It is also the first to relate the effect of gender in lung fibrosis with polymorphisms in AGT.

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Genotyping at −18 revealed a lack of diversity at this position, therefore, it was excluded from this study.

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Titel: Angiotensinogen Promoter Polymorphisms Predict Low Diffusing Capacity in U.S. and Spanish IPF Cohorts
verfasst von: My-Trang T. Dang
Chenyang Gu
Jeannie I. Klavanian
Katherine A. Jernigan
Karen H. Friderici
Yuehua Cui
Maria Molina-Molina
Julio Ancochea
Antoni Xaubet
Bruce D. Uhal
Publikationsdatum: 01.08.2013
Verlag: Springer US
Erschienen in: Lung / Ausgabe 4/2013
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-013-9476-2

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Angiotensinogen Promoter Polymorphisms Predict Low Diffusing Capacity in U.S. and Spanish IPF Cohorts