RT Journal Article
SR Electronic
T1 Polymorphic markers of the fibrillin-1 gene and systemic sclerosis in European Caucasian patients.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 643
OP 649
VO 35
IS 4
A1 Julien Wipff
A1 Matthieu Giraud
A1 Jean Sibilia
A1 Luc Mouthon
A1 Olivier Meyer
A1 Kiet Tiev
A1 Paolo Airo
A1 Paola Caramaschi
A1 Serena Guiducci
A1 Henri Jean Garchon
A1 Marco Matucci-Cerinic
A1 André Kahan
A1 Jéröme Avouac
A1 Catherine Boileau
A1 Yannick Allanore
YR 2008
UL http://www.jrheum.org/content/35/4/643.abstract
AB 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. CONCLUSION: 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.