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

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.