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Rheumatology Advance Access published online on April 16, 2008
Rheumatology, doi:10.1093/rheumatology/ken125
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Associations of DNase IV polymorphisms with autoantibodies in patients with systemic lupus erythematosus

I. Kim1, N. W. Hur1, H. D. Shin2, B. L. Park2, H. S. Cheong2 and S.-C. Bae1

1Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Hanyang University and 2Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea.

Correspondence to: S.-C. Bae, The Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul 133-792, Korea. E-mail: scbae{at}hanyang.ac.kr


  Abstract

Objectives. The aim of this study was to investigate genetic polymorphisms of DNase IV and their relationship with SLE and various autoantibodies present in SLE patients.

Methods. A total of 532 SLE patients and 521 healthy controls belonging to the Korean population were enrolled into this study. Sequencing of the entire coding region of the DNase IV gene (including the promoter region) was carried out using a DNA analyser. Autoantibodies including anti-Sm, anti-Ro, anti-La, anti-RNP and anti-dsDNA were determined either by indirect immunofluorescence or double immunodiffusion methods. Multiple logistic regression analysis was performed to examine the genetic association with SLE and autoantibodies.

Results. We found three single-nucleotide polymorphisms (SNPs): –2753G->A, +147T->G (Gly49Gly) and +1466G->T. The –2753G->A and +147T->G (Gly49Gly) SNPs were selected for larger scale genotyping based on linkage disequilibria and haplotype-tagging status. Although the –2753G->A SNP was more common than the +147T->G (Gly49Gly) SNP (frequencies: 0.330 and 0.002, respectively), its association with the risk of SLE was not statistically significant. However, –2753G->A SNP was significantly associated with the production of anti-Sm antibody [odds ratio (95% CI): co-dominant model, 1.89 (1.28–2.79); dominant model, 2.17 (1.20–3.90) and recessive model, 2.62 (1.33–5.17)].

Conclusions. We did not find significant relationships between DNase IV polymorphisms and the risk of SLE, but the association of the common –2753G->A allele in the promoter region with the production of anti-Sm antibody implicates DNase IV as a putative candidate gene of SLE.

KEY WORDS: DNase IV, Single-nucleotide polymorphism, Systemic lupus erythematosus

Submitted 18 July 2007; revised version accepted 25 February 2008.
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