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.