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.
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▸ Supplementary data are published online only athttp://ard.bmj.com/content/vol68/issue9
Funding The work was supported by grants from the German Ministry for Research and Education (Interdisziplinares Zentrum für Klinische Forschung Leipzig, Teilprojekt A21) and the “German Competence Network Rheumatology”, grant 01 GI 9955).
Competing interests None.
Ethics approval Approved by the University of Leipzig’s ethics committee.