Association Analysis of Polymorphism in Slc22a4 and Runx1 with Rheumatoid Arthritis Susceptibility and Disease Severity in a Korean Population

Abstract

PURPOSE: Two single-nucleotide polymorphisms (SNPs) in the SLC22A4 (organic cation transporter 1, OCTN1) gene and one SNP in the RUNX1 (Runt-related transcription factor 1) gene were recently reported to be associated with susceptibility to rheumatoid arthritis (RA) in a Japanese population, but the SLC22A4 SNPs did not show association in Canadian and Caucasian populations. In this study we investigated genetic association of the SNPs in the SLC22A4 and RUNX1 genes with RA susceptibility and radiographic severity in a Korean population. METHODS: The SLC22A4 SNPs were slc2F1 [rs2073838] and slc2F2 [rs3792876], whereas the RUNX1 SNP was runx1 [rs2268277]. The three SNPs were genotyped in 1076 unrelated RA patients (classified in 4 severity stages) and 704 controls using the MassARRAYTM genotyping system. We calculated odds ratios and P-values as controlling age, sex, disease duration and HLA-DRB1 genotype as co-variables in multivariate logistic regressions. RESULTS: None of the three SNPs showed genotypic association with RA susceptibility. In contrast, the SLC22A4 SNP slc2F1 was significantly associated with RA-radiographic severity in a dominant model (P = 0.035, OR = 1.53, 95% CI = 1.03-2.26). The other SLC22A4 SNP slc2F2 also showed a marginal association level (P = 0.059, OR = 1.46, 95% CI = 0.99-2.16), and the two SNPs were in strong linkage disequilibrium (Δ > 0.99) between each other in Koreans similarly to the Japanese (Δ > 0.97). The RUNX1 SNP runx1 was not associated with RA severity though. CONCLUSIONS: The associations of SLC22A4 and RUNX1 SNPs with RA susceptibility were not replicated in Koreans, but the SNPs in SLC22A4 appear to be associated with radiographic severity in Koreans.