Objectives: To analyze the distribution of single nucleotide polymorphisms (SNP’s) in the 5’ regulatory region of the DNASE2 gene, in patients with rheumatoid arthritis (RA) and healthy controls.
Methods: A total of 906 RA patients 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 RA patients compared to healthy controls. The strongest association was found for the -1066 G allele (33.5% vs. 27.2%, p = 0.007, odds ratio 1.34). Homozygosity for this allele (genotype GG) resulted in an additional increase in disease susceptibility (12.5% vs. 6.2%, odds ratio 2.17). The association was replicated in a second case–control series of 483 RA patients from two German multi-center 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-CCP 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 SNP’s 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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