title: Angiotensin-converting enzyme 2 (ACE2) haplotypes are associated with pulmonary disease phenotypes in sarcoidosis patients.
abstract: OBJECTIVE
  Angiotensin II (Ang II) formation by angiotensin-converting enzyme (ACE) or other enzymes has shown to exhibit profibrotic properties in a variety of fibrotic diseases. A homologue of ACE called ACE2 has been shown to counteract the formation of Ang II. Genetic variation in the components involved in Ang II formation may underlie the progression of pulmonary sarcoidosis.
  
  
  METHODS
  Seven ACE2 SNPs, located on the X-chromosome, were investigated using SSP-PCR and haplotypes were constructed. Gender-matched analyses of sarcoidosis patients (80 males/64 females) and controls (110 males/218 females) were performed to correlate disease susceptibility and pulmonary disease phenotypes with ACE2 genotypes and haplotypes.
  
  
  RESULTS
  ACE2 SNPs or haplotypes were not associated with susceptibility for sarcoidosis. Haplotype 4 was only present in sarcoid males without parenchymal involvement (frequency: 0.19) and absent in males with parenchymal involvement (p = 0.006; pcorr. = 0.05; degrees of freedom (df) = 1; OR = 0). No significant difference was observed between haplotype 4 frequencies in females with (0.08) or without (0.13) parenchymal involvement (p = 0.5). Although not significant after correction, analysis of the patient group with fibrosis showed that males with haplotype 5 (0.27) were predominant over those with haplotype 5 of the groups without fibrosis (0.03); p = 0.01; pc = 0.08; df = 1; OR = 11.4. Females with fibrosis vs. no fibrosis revealed no difference between haplotype 5 frequencies: 0.05 vs. 0.03; p = 0.37; pc = 1; df = 1.
  
  
  CONCLUSIONS
  These results suggest that ACE2 might be involved in the progression of pulmonary sarcoidosis which may depend on gender. Subsequent studies using larger groups are needed to confirm these findings.
authors.affiliation: Heart Lung Centre Utrecht, St. Antonius Hospital, Department of Pulmonology, Nieuwegein, The Netherlands.
authors.forename: Adrian
authors.initials: A
authors.lastname: Kruit
authors.forename: Henk J T
authors.initials: HJ
authors.lastname: Ruven
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
authors.forename: Jules M M
authors.initials: JM
authors.lastname: van den Bosch
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D002268:Carboxypeptidases / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D017565:Sarcoidosis, Pulmonary / Q000201:enzymology* / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2