|Title||Angiotensinogen promoter polymorphisms predict low diffusing capacity in U.S. and Spanish IPF cohorts|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Dang M-TT, Gu C, Klavanian JI, Jernigan KA, Friderici KH, Cui Y, Molina-Molina M, Ancochea J, Xaubet A, Uhal BD|
|Date Published||2013 Aug|
|Keywords||Aged, 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|
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.
|PubMed Central ID||PMC4476508|
|Grant List||HL-45136 / HL / NHLBI NIH HHS / United States |
R01 HL045136 / HL / NHLBI NIH HHS / United States