Περίληψη:
Genetic variation in the interferon regulatory factor 5 (IRF5) gene
affects systemic lupus erythematosus (SLE) susceptibility. However,
association is complex and incompletely defined. We obtained fourteen
European sample collections with a total of 1383 SLE patients and 1614
controls to better define the role of the different IRF5 variants.
Eleven polymorphisms were studied, including nine tag single nucleotide
polymorphisms (SNPs) and two extra functional polymorphisms. Two tag
SNPs showed independent and opposed associations: susceptibility
(rs10488631, P < 10(-17)) and protection (rs729302, P < 10(-6)).
Haplotype analyses showed that the susceptibility haplotype, identified
by the minor allele of rs10488631, can be due to epistasis between three
IRF5 functional polymorphisms. These polymorphisms determine increased
mRNA expression, a splice variant with a different exon 1 and a longer
proline-rich region in exon 6. This result is striking as none of the
three polymorphisms had an independent effect on their own. Protection
was independent of these polymorphisms and seemed to reside in the 50
side of the gene. In conclusion, our results help to understand the role
of the IRF5 locus in SLE susceptibility by clearly separating protection
from susceptibility as caused by independent polymorphisms. In addition,
we have found evidence for epistasis between known functional
polymorphisms for the susceptibility effect.
Συγγραφείς:
Ferreiro-Neira, I.
Calaza, M.
Alonso-Perez, E.
Marchini, M.
and Scorza, R.
Sebastiani, G. D.
Blanco, F. J.
Rego, I. and
Pullmann, Jr., R.
Pullmann, R.
Kallenberg, C. G.
Bijl, M.
and Skopouli, F. N.
Mavromati, M.
Migliaresi, S.
Barizzone,
N.
Ruzickova, S.
Dostal, C.
Schmidt, R. E.
Witte, T. and
Papasteriades, C.
Kappou-Rigatou, I.
Endreffy, E.
Kovacs, A.
and Ordi-Ros, J.
Balada, E.
Carreira, P.
Gomez-Reino, J. J.
and Gonzalez, A.
