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Open Access Research article

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

Klaus Stark1, Jozef Rovenský2, Stanislava Blažičková2, Hans Grosse-Wilde3, Stanislav Ferencik3, Christian Hengstenberg1 and Rainer H Straub4*

Author Affiliations

1 Department of Internal Medicine II, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany

2 National Institute of Rheumatic Diseases, Nabr. I. Krasku 4, 921 23 Piešt'any, Slovakia

3 Institute of Immunology, University Hospital of Essen, Virchowstrasse 179, 45122 Essen, Germany

4 Department of Internal Medicine I, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany

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Arthritis Research & Therapy 2009, 11:R70  doi:10.1186/ar2699

Published: 15 May 2009

Abstract

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 rs7574865STAT4 (P = 9.2*10-6; OR = 1.71, 95% CI = 1.35 – 2.18) and rs2476601PTPN22 (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 (Pcorr = 0.114 and Pcorr = 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.