Homozygosity for DNASE2 single nucleotide polymorphisms in the 5′-regulatory region is associated with rheumatoid arthritis. Issue 9 (23rd September 2008)

• Record Type: Journal Article
• Authors: Rossol, M; Pierer, M; Arnold, S; Keyßer, G; Burkhardt, H; Baerwald, C; Wagner, U
• Is Part Of: Annals of the rheumatic diseases. Volume 68:Issue 9(2009)
• Page Start: 1498
• Page End: 1503
• Publication Date: 2008-09-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2008.092239
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: To analyse the distribution of single nucleotide polymorphisms (SNPs) in the 5′-regulatory region of the DNASE2 gene, in patients with rheumatoid arthritis (RA) and healthy controls. Methods: A total of 906 patients with RA and 878 healthy controls were genotyped. All subjects were of German Caucasian origin. Genotyping was performed by real-time polymerase chain reaction technology, using a TaqMan 5′-allele discrimination assay. Results: In the initial analysis of unrelated case–control samples, three DNASE2 SNP alleles in the 5′-regulatory region were significantly more frequent in patients with RA than in healthy controls. The strongest association was found for the −1066G allele (33.5% vs 27.2%, p = 0.007, odds ratio (OR) = 1.34). Homozygosity for this allele (genotype GG) resulted in an additional increase in disease susceptibility (12.5% vs 6.2%, OR = 2.17). The association was replicated in a second case–control series of 483 patients with RA from two German multicentre studies and 474 controls. The association of DNASE2 −1066 GG homozygosity with RA was limited to rheumatoid factor-positive disease, but was not influenced by the presence of anti-cyclic citrullinated peptide or antinuclear antibodies. Similarly, the presence or absence of the HLA-DRB1 shared epitope or the RA-associated PTPN22 allele had no influence on this association. Conclusions: The association of SNPs in the 5′-regulatory region of the DNA degrading enzyme DNASE2 with RA implies a role for this enzyme in the pathogenesis of this autoimmune disease.