title: Angiotensinogen promoter polymorphisms predict low diffusing capacity in U.S. and Spanish IPF cohorts.
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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA.
authors.forename: My-Trang T
authors.initials: MT
authors.lastname: Dang
authors.forename: Chenyang
authors.initials: C
authors.lastname: Gu
authors.forename: Jeannie I
authors.initials: JI
authors.lastname: Klavanian
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Jernigan
authors.forename: Karen H
authors.initials: KH
authors.lastname: Friderici
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Cui
authors.forename: Maria
authors.initials: M
authors.lastname: Molina-Molina
authors.forename: Julio
authors.initials: J
authors.lastname: Ancochea
authors.forename: Antoni
authors.initials: A
authors.lastname: Xaubet
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Uhal
mesh_terms: D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000503:physiopathology; D016013:Likelihood Functions; D016015:Logistic Models; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011653:Pulmonary Diffusing Capacity / Q000235:genetics*; D012737:Sex Factors; D013030:Spain; D014481:United States; D014797:Vital Capacity / Q000235:genetics
chemical_list: C534931:AGT protein, human; D000808:Angiotensinogen