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Rheumatology Advance Access published online on January 31, 2006
Rheumatology, doi:10.1093/rheumatology/kel019
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 5, 2005
Accepted December 16, 2005

Original Article

Association of a non-synonymous single-nucleotide polymorphism of DNASEI with SLE susceptibility

A. Bodaño 1, A. González 1, I. Ferreiros-Vidal 1, E. Balada 2, J. Ordi 2, P. Carreira 3, J. J. Gómez-Reino 4, and C. Conde 1 *

1 Research Laboratory and Rheumatology Unit, Hospital Clinico Universitario de Santiago de Compostela, Spain
2 Internal Medicine, Research Laboratory in Autoimmune Diseases, Hospital Vall d'Hebron, Barcelona
3 Rheumatology Unit, Hospital 12 de Octubre, Madrid, Spain
4 Research Laboratory and Rheumatology Unit, Hospital Clinico Universitario de Santiago de Compostela, Spain; Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain

* To whom correspondence should be addressed.
C. Conde, E-mail: Carmen.Conde.Muro{at}sergas.es


  Abstract

Objectives. To investigate the association of a non-synonymous single-nucleotide polymorphism (SNP) in DNASEI with susceptibility to systemic lupus erythematosus (SLE) and the production of autoantibodies to nuclear antigens.

Methods. The Gln244Arg (rs1053874) SNP was studied in 276 SLE patients and in 368 healthy controls of Spanish ancestry. Its relationship with SLE susceptibility, serum DNase I activity, anti-ribonucleoprotein (RNP), anti-double-stranded DNA (dsDNA), anti-nucleosome and anti-single-stranded DNA (ssDNA) antibodies was determined.

Results. An association of the Gln244Arg SNP with SLE susceptibility that followed a recessive genetic model (P=0.002) was found. The GG genotype was more common in SLE patients (59.8%) than in controls (47.3%). However, the Gln244Arg genotype did not correlate with DNase I activity in sera from SLE patients or from controls. In addition, the Gln244Arg SNP did not influence autoantibody titres significantly.

Conclusion. The association of the Gln244Arg SNP with SLE susceptibility indicates that common polymorphisms in DNASEI play a role in the genetics of SLE. However, the lack of effect of the Gln244Arg SNP on serum DNase I activity calls into question the direct involvement of this specific SNP.

Keywords: Systemic lupus erythematosus; Single-nucleotide polymorphism.; DNASEI gene; autoantibodies.
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