Περίληψη:
Introduction: Systemic Lupus Erythematosus (SLE) shows a spectrum of
clinical manifestations that complicate its diagnosis, treatment and
research. This variability is likely related with environmental
exposures and genetic factors among which known SLE susceptibility loci
are prime candidates. The first published analyses seem to indicate that
this is the case for some of them, but results are still inconclusive
and we aimed to further explore this question.
Methods: European SLE patients, 1444, recruited at 17 centres from 10
countries were analyzed. Genotypes for 26 SLE associated SNPs were
compared between patients with and without each of 11 clinical features:
ten of the American College of Rheumatology (ACR) classification
criteria (except ANAs) and age of disease onset. These analyses were
adjusted for centre of recruitment, top ancestry informative markers,
gender and time of follow-up. Overlap of samples with previous studies
was excluded for assessing replication.
Results: There were three new associations: the SNPs in XKR6 and in
FAM167A-BLK were associated with lupus nephritis (OR = 0.76 and 1.30,
P-corr = 0.007 and 0.03, respectively) and the SNP of MECP2, which is in
chromosome X, with earlier age of disease onset in men. The previously
reported association of STAT4 with early age of disease onset was
replicated. Some other results were suggestive of the presence of
additional associations. Together, the association signals provided
support to some previous findings and to the characterization of lupus
nephritis, autoantibodies and age of disease onset as the clinical
features more associated with SLE loci.
Conclusion: Some of the SLE loci shape the disease phenotype in addition
to increase susceptibility to SLE. This influence is more prominent for
some clinical features than for others. However, results are only
partially consistent between studies and subphenotype specific GWAS are
needed to unravel their genetic component.
Συγγραφείς:
Alonso-Perez, Elisa
Suarez-Gestal, Marian
Calaza, Manuel and
Ordi-Ros, Josep
Balada, Eva
Bijl, Marc
Papasteriades,
Chryssa
Carreira, Patricia
Skopouli, Fotini N.
Witte,
Torsten
Endreffy, Emoeke
Marchini, Maurizio
Migliaresi,
Sergio
Sebastiani, Gian Domenico
Santos, Maria Jose
Suarez,
Ana
Blanco, Francisco J.
Barizzone, Nadia
Pullmann, Rudolf
and Ruzickova, Sarka
Lauwerys, Bernard R.
Gomez-Reino, Juan J.
and Gonzalez, Antonio
European Consortium SLE DNA Collec
