title: Polymorphic markers of the fibrillin-1 gene and systemic sclerosis in European Caucasian patients.
abstract: OBJECTIVE
  Evidence suggests that systemic sclerosis (SSc) belongs to the fibrillinopathic disorders. Significant associations have been found with the fibrillin-1 gene (FBN1) in Choctaw and Japanese populations. We investigated FBN1 polymorphisms in cohorts of European Caucasian patients.
  
  
  METHODS
  We investigated 6 FBN1 polymorphisms in 2 cohorts: one with 399 French subjects (243 SSc patients/156 matched healthy controls), another with 319 Italian subjects (266 SSc patients/153 matched healthy controls). The 6 FBN1 polymorphisms included one single-nucleotide polymorphism (SNP) in intron C to replicate its genetic association and 5 microsatellite markers (D15S1028 in the 5' region, intragenic MTS2 and MTS3, and D15S123 and D15S143 in the 3' region). Then we investigated the French cohort enlarged to 362 SSc patients/162 matched healthy controls for 5 tagging single nucleotide polymorphisms (tagSNP) that account for the common genetic diversity according to HapMap data. We used Arlequin, Cocaphase, Phase 2 software, and Fisher's exact test for statistical analyses.
  
  
  RESULTS
  All markers were in Hardy-Weinberg equilibrium. No association was detected between polymorphic markers and disease in either the French or Italian cohorts, even for specific phenotypes. No significant differences between patients and controls were detected for the 5 tagSNP.
  
  
  CONCLUSIONS
  In contrast with data from Choctaw and Japanese patients, no association was detected between the polymorphic markers of FBN1 and SSc in 2 European Caucasian populations. These discrepancies may be explained by ethnic specificities and heterogeneity associated with this multigenic disease.
authors.affiliation: Department of Rheumatology A, Paris Descartes University, Medical Faculty, Cochin Hospital, AP-HP, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Wipff
authors.forename: Matthieu
authors.initials: M
authors.lastname: Giraud
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: Kiet
authors.initials: K
authors.lastname: Tiev
authors.forename: Paolo
authors.initials: P
authors.lastname: Airo
authors.forename: Paola
authors.initials: P
authors.lastname: Caramaschi
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Henri Jean
authors.initials: HJ
authors.lastname: Garchon
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.forename: André
authors.initials: A
authors.lastname: Kahan
authors.forename: Jéröme
authors.initials: J
authors.lastname: Avouac
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D002874:Chromosome Mapping; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D044465:White People / Q000235:genetics*; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D005819:Genetic Markers; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines