title: Associations of DNase IV polymorphisms with autoantibodies in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Seoul, Korea.
authors.forename: I
authors.initials: I
authors.lastname: Kim
authors.forename: N W
authors.initials: NW
authors.lastname: Hur
authors.forename: H D
authors.initials: HD
authors.lastname: Shin
authors.forename: B L
authors.initials: BL
authors.lastname: Park
authors.forename: H S
authors.initials: HS
authors.lastname: Cheong
authors.forename: S-C
authors.initials: SC
authors.lastname: Bae
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology; D002874:Chromosome Mapping / Q000379:methods; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D045585:Flap Endonucleases; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D055517:snRNP Core Proteins
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D005090:Exodeoxyribonucleases; D045585:Flap Endonucleases