AN HERV-LTR ELEMENT AT THE DQB1 LOCUS MODIFIES SUSCEPTIBILITY AMONG
HLA-DRB1*04 - DQB1*0301/0302 POSITIVE PATIENTS WITH RHEUMATOID ARTHRITIS.
C Seidl1, H Donner2, E Petershofen1,
K-H Usadel2, E Seifried1, JP Kaltwasser2,
and K Badenhoop2, 1Institute of Transfusion Medicine
and Immunohematology, RCBDS and 2the Departments of Rheumatology
and Endocrinology, Center of Internal Medicine, JW Goethe-University Frankfurt,
Germany.
Human endogenous retrovirus (HERV) long terminal repeat
(LTR) elements contain regulatory sequences that can influence the expression
of adjacent cellular genes, which may contribute to (auto)immune disease.
Rheumatoid arthritis (RA) is associated with particular HLA-DR/DQ haplotypes
that modulate the immunopathogenesis of this autoimmune disease. We have
therefore studied a LTR element (DQ-LTR) of the HERV-K family at the DQB1
locus, for a possible disease association among 228 RA patients and 341
unrelated blood donors. Analysis of the DQ-LTR element was performed by
nested PCR amplification of genomic DNA. The DQ-LTR element was significantly
overrepresentated among patients (76% vs 33%, P<0.0002), with the majority
of patients being heterozygous for the DQ-LTR (61% vs 22%, P<0.001).
Patients carrying either the HLA-DRB1*04-DQB1*0301 (71% vs 46%, P=0.02)
or the HLA-DRB1*04-DQB1*0302 (97% vs 83%, P=0.0025) haplotype were characterised
by an increase of the DQ-LTR in comparison to matched controls. In conclusion,
these data suggest that this DQ-LTR modifies the genetic risk among DRB1*04-DQB1*0301/0302
positive RA patients.