title: Association between an endoglin gene polymorphism and systemic sclerosis-related pulmonary arterial hypertension.
abstract: Systemic sclerosis (SSc) is a connective tissue disorder characterized by early generalized microangiopathy with disturbed angiogenesis. Endoglin gene (ENG) encodes a transmembrane glycoprotein which acts as an accessory receptor for the transforming growth factor-beta (TGF-beta) superfamily, and is crucial for maintaining vascular integrity. A 6-base insertion in intron 7 (6bINS) of ENG has been reported to be associated with microvascular disturbance.
  
  
  OBJECTIVE
  Our objective was to investigate the relationship between 6bINS and the vascular complication pulmonary arterial hypertension (PAH) in SSc in a French Caucasian population.
  
  
  METHODS
  Two hundred eighty SSc cases containing 29/280 having PAH diagnosed by catheterism were compared with 140 patients with osteoarthritis. Genotyping was performed by polymerase-chain-reaction-based fluorescence and direct sequencing of genomic DNA.
  
  
  RESULTS
  The polymorphism was in Hardy-Weinberg equilibrium. We observed a significant lower frequency of 6bINS allele in SSc patients with associated PAH compared with controls [10.3 vs 23.9%, P = 0.01; odds ratio (OR) 0.37, 95% confidence interval (CI) 0.15-0.89], and a trend in comparison with SSc patients without PAH (10.3 vs 20.3%, P = 0.05; OR: 0.45, 95% CI: 0.19-1.08). Genotypes carrying allele 6bINS were also less frequent in SSc patients with PAH than in controls (20.7 vs 42.9%, P = 0.02).
  
  
  CONCLUSIONS
  Thus the frequency of 6bINS differs between SSc patients with or without PAH, suggesting the implication of ENG in this devastating vascular complication of SSc.
authors.affiliation: René Descartes University, Medical Faculty, Rheumatology A Department, Cochin Hospital, AP-HP, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Wipff
authors.forename: A
authors.initials: A
authors.lastname: Kahan
authors.forename: E
authors.initials: E
authors.lastname: Hachulla
authors.forename: J
authors.initials: J
authors.lastname: Sibilia
authors.forename: J
authors.initials: J
authors.lastname: Cabane
authors.forename: O
authors.initials: O
authors.lastname: Meyer
authors.forename: L
authors.initials: L
authors.lastname: Mouthon
authors.forename: L
authors.initials: L
authors.lastname: Guillevin
authors.forename: C
authors.initials: C
authors.lastname: Junien
authors.forename: C
authors.initials: C
authors.lastname: Boileau
authors.forename: Y
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D000071063:Endoglin; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000150:complications / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface