Angiotensinogen promoter polymorphisms predict low diffusing capacity in U.S. and Spanish IPF cohorts

TitleAngiotensinogen promoter polymorphisms predict low diffusing capacity in U.S. and Spanish IPF cohorts
Publication TypeJournal Article
Year of Publication2013
AuthorsDang M-TT, Gu C, Klavanian JI, Jernigan KA, Friderici KH, Cui Y, Molina-Molina M, Ancochea J, Xaubet A, Uhal BD
JournalLung
Volume191
Issue4
Pagination353-60
Date Published2013 Aug
ISSN1432-1750
KeywordsAged, Angiotensinogen, Chi-Square Distribution, Female, Forced Expiratory Volume, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, Homozygote, Humans, Idiopathic Pulmonary Fibrosis, Likelihood Functions, Logistic Models, Lung, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Pulmonary Diffusing Capacity, Sex Factors, Spain, United States, Vital Capacity
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.

DOI10.1007/s00408-013-9476-2
Alternate JournalLung
PubMed ID23715995
PubMed Central IDPMC4476508
Grant ListHL-45136 / HL / NHLBI NIH HHS / United States
R01 HL045136 / HL / NHLBI NIH HHS / United States