Association of common polymorphisms in known susceptibility genes with rheumatoid arthritis in a Slovak population using osteoarthritis patients as controls

INTRODUCTION: Both genetic and environmental factors contribute to rheumatoid arthritis (RA), a common and complex autoimmune disease. As well as the major susceptibility gene HLA-DRB1, recent genome-wide and candidate-gene studies reported additional evidence for association of single nucleotide polymorphism (SNP) markers in the PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5 loci with RA. This study was initiated to investigate the association between defined genetic markers and RA in a Slovak population. In contrast to recent studies, we included intensively-characterized osteoarthritis (OA) patients as controls. METHODS: We used material of 520 RA and 303 OA samples in a case-control setting. Six SNPs were genotyped using TaqMan assays. HLA-DRB1 alleles were determined by employing site-specific polymerase chain reaction (PCR) amplification. RESULTS: No statistically significant association of TRAF1/C5 SNPs rs3761847 and rs10818488 with RA was detected. However, we were able to replicate the association signals between RA and HLA-DRB1 alleles, STAT4 (rs7574865), PTPN22 (rs2476601) and OLIG3/TNFAIP3 (rs10499194 and rs6920220). The strongest signal was detected for HLA-DRB1*04 with an allelic P = 1.2*10(-13 )(OR = 2.92, 95% confidence interval (CI) = 2.18 – 3.91). Additionally, SNPs rs7574865(STAT4 )(P = 9.2*10(-6); OR = 1.71, 95% CI = 1.35 – 2.18) and rs2476601(PTPN22 )(P = 9.5*10(-4); OR = 1.67, 95% CI = 1.23 – 2.26) were associated with susceptibility to RA, whereas after permutation testing OLIG3/TNFAIP3 SNPs rs10499194 and rs6920220 missed our criteria for significance (P(corr )= 0.114 and P(corr )= 0.180, respectively). CONCLUSIONS: In our Slovak population, HLA-DRB1 alleles as well as SNPs in STAT4 and PTPN22 genes showed a strong association with RA.