title: Angiotensin-converting enzyme gene does not contribute to genetic susceptibility to systemic sclerosis in European Caucasians.
abstract: OBJECTIVE
  To determine whether angiotensin-converting enzyme (ACE) polymorphisms including I/D and 2 single-nucleotide polymorphisms (SNP) affect susceptibility to systemic sclerosis (SSc) in a large French Caucasian population.
  
  
  METHODS
  A case-control study was performed in 494 patients with SSc and 280 healthy controls for I/D polymorphism. Two supplementary exonic SNP of ACE gene (rs4309, rs4362) were genotyped in 659 patients with SSc and 511 matched healthy controls. Among the whole SSc population, 453 (67%) patients with SSc had the limited cutaneous subtype, 47 (7%) had precapillary pulmonary arterial hypertension, 209 (32%) had digital ulcers, and 10 (1.5%) had renal crisis. A combined analysis of the available results for ACE I/D genotypes in Caucasians was also performed.
  
  
  RESULTS
  There was no association between the 3 polymorphic markers and SSc for allelic and genotype frequencies. No association was observed for the different vascular subsets of the disease. Haplotype analyses did not detect any association. The lack of association for ACE I/D was confirmed by the combined analysis.
  
  
  CONCLUSIONS
  These results in a large cohort of European Caucasian patients with SSc do not support that the ACE gene is implicated in the pathogenesis of SSc and its vascular damage.
authors.affiliation: Paris Descartes Université, Rhumatologie A, Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Wipff
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gallier
authors.forename: Philippe
authors.initials: P
authors.lastname: Dieude
authors.forename: Jerome
authors.initials: J
authors.lastname: Avouac
authors.forename: Kiet
authors.initials: K
authors.lastname: Tiev
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.forename: Brigitte
authors.initials: B
authors.lastname: Granel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Diot
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.forename: Olivier
authors.initials: O
authors.lastname: Meyer
authors.forename: Andre
authors.initials: A
authors.lastname: Kahan
authors.forename: Mathilde
authors.initials: M
authors.lastname: Varret
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015897:Comorbidity; D004252:DNA Mutational Analysis; D005060:Europe / Q000208:ethnology; D005260:Female; D005602:France / Q000208:ethnology; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D007674:Kidney Diseases / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012083:Renin / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D044465:White People
chemical_list: D005819:Genetic Markers; D012083:Renin