Possible association of the X-ray cross complementing gene 1 (XRCC1) Arg280His polymorphism as a risk for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the invasion of synovial cells into cartilage and bone, exhibiting certain features of transformed cells. To examine whether retardation of DNA repair pathway of oxidative damage is a possible mechanism in altered phenotypes of these cells, we analyzed SNPs of the base excision repair (BER) protein, X-ray repair cross complementing gene 1 (XRCC1), among RA patients. Genomic DNA was extracted from blood cells of 40 RA patients and SNPs of the three allele of the XRCC1 coding region (codons 194, 280 and 399) were determined by PCR, followed by sequencing. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased RA risk (odds ratio 13; 95% confidence interval 1.1-147) after adjustment for smoking. These data provide evidence for the first time that BER, which is involved in the recovery from oxidative damage, may correlate with RA.