Polymorphic markers of the fibrillin-1 gene and systemic sclerosis in European Caucasian patients.
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.
Wipff
Julien
J
Department of Rheumatology A, Paris Descartes University, Medical Faculty, Cochin Hospital, AP-HP, Paris, France.
Giraud
Matthieu
M
Sibilia
Jean
J
Mouthon
Luc
L
Meyer
Olivier
O
Tiev
Kiet
K
Airo
Paolo
P
Caramaschi
Paola
P
Guiducci
Serena
S
Garchon
Henri Jean
HJ
Matucci-Cerinic
Marco
M
Kahan
André
A
Avouac
Jéröme
J
Boileau
Catherine
C
Allanore
Yannick
Y
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
D000071838:Fibrillin-1; D000071837:Fibrillins; D005819:Genetic Markers; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines