Rheumatol Int DOI 10.1007/s00296-010-1725-6 123 ORIGINAL ARTICLE Rheumatoid arthritis risk associates with DNA repair gene XRCC1 Arg399Gln polymorphism in Turkish patients Elif Yosunkaya · Funda Karakurt · Esra Cetin · Levent Ozgonenel · Ilhan Onaran · Bahadir Batar · Mehmet Guven · Gonul Kanigur Sultuybek Received: 18 June 2010 / Accepted: 30 December 2010  Springer-Verlag 2011 Abstract Rheumatoid arthritis (RA) is an autoinXamma- tory disease with a genetic background. The synoviocytes in RA shows cellular transformation with tumor-like fea- tures, and RA patients have genomic instability and relaxa- tion of DNA repair mechanisms. The polymorphisms in BER repair pathway genes, XRCC1 and OGG1, may change the response to inXammation via altered DNA repair capacity. In this study, we aimed to investigate the relationship between the risk of RA and XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymor- phisms in a group of Turkish RA patients. XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymor- phisms were investigated by PCR–RFLP method in 100 RA patients and 158 healthy control subjects. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% conWdence intervals (95% CI) using the  2 -tests. RA patients in this study had signiWcantly higher frequencies of XRCC1 Arg399Gln polymorphism in both homozygote (GG) (35%, OR: 7.78 [95% CI: 3.65– 16.59], P < 0.001) and heterozygote (AG) forms (41%, OR: 2.17 [95% CI: 1.19–3.96], P < 0.01) and also increased frequency of 399Gln (G) allele (55%, OR:2.99 [95% CI: 1.67–5.37], P < 0.001). We conclude that XRCC1 Arg194Trp, and OGG1 Ser326Cys polymorphisms are not associated with RA; however, Arg399Gln polymorphism is a signiWcant risk factor of RA, and carriers of 399Gln (G) allele have greater risk of RA. Keywords Rheumatoid arthritis · XRCC1 · OGG1 · Polymorphism Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease with an estimated prevalence of 0.8–1% [1]. The altered immune response and synovial hyperplasia leading to irre- versible joint damage characterize the disease. Fibroblast- like synoviocytes exhibiting certain features of cellular transformation proliferate autonomously and ultimately lead to hyperplasia of the synovium. DNA damage caused by excessive reactive oxygen species (ROS) produced during cellular oxidative phosphorylation underlies cellular trans- formation, as ROS damages matrix components and signals for ampliWcation of the synovial inXammatory–proliferative response [2]. The rheumatoid synovium can be viewed as a multicentric tumor-like mass that invades and destroys its local environs, revealed by H-ras and p53 mutations in syno- viocytes. In addition to a high degree of genomic instability in the synovium, there is also relaxation of DNA repair mechanisms in RA [3]. In recent years, with the availability of microarray platforms and next-generation sequencing, the list of RA susceptibility loci has greatly expanded. The majority of SNP markers associated with the disease belongs to genes acting in apoptosis, signaling pathways, and immune regulation such as T-cell activation, while the larg- est contribution still remains to be the HLA-DRB1 locus [4]. E. Yosunkaya (&) Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Selamicesme Goktepe sok. No:3/26 Kadikoy, Istanbul, Turkey e-mail: yosunkayafenerci@hotmail.com; eyfenerci@istanbul.edu.tr F. Karakurt · E. Cetin · L. Ozgonenel Department of Physical Medicine and Rehabilitation, S.B. Ãstanbul Education and Research Hospital, Istanbul, Turkey I. Onaran · B. Batar · M. Guven · G. K. Sultuybek Department of Medical Biology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey