Natural resistance-associated macrophage protein 1 gene polymorphisms in rheumatoid arthritis

OBJECTIVES: To investigate the association of natural resistance-associated macrophage protein 1 gene (NRAMP1) polymorphisms with rheumatoid arthritis (RA) in Taiwan. METHODS: NRAMP1 polymorphisms were determined from 113 RA patients and 74 healthy controls using the polymerase chain reaction/restriction fragment length polymorphism method. RESULTS: The genotype frequencies of NRAMP1 823 C/C, 1703G/G (543D/D), and 1729+55 del 4 TGTG+/+ (244/244) were significantly higher in patients with RA than in controls. Similar findings were also evident in allele frequencies and allele carriage frequencies of 823C, 1703G (543D), and 1729+55 del 4 TGTG+ (244). The associations of these polymorphisms with RA were independent of HLA-DR4. Linkage disequilibria could be found between 823C and 1703G, and between 1703G and 1729+55 del 4 TGTG+. The estimated haplotype frequency of NRAMP1 823C/1703G/1729+55 del 4 TGTG+ was significantly increased in RA patients compared with controls. We also found that patients with 823 C/C had a significantly lower prevalence of rheumatoid nodule than those without 823 C/C. CONCLUSION: NRAMP1 823C, 1703G (543D), and 1729+55 del 4 TGTG+ (244) are precipitating factors for the development of RA in Taiwan. The estimated NRAMP1 823C/1703G/1729+del 4 TGTG+ haplotype is associated with susceptibility to RA. NRAMP1 823 C/C prevents the development of rheumatoid nodule in RA patients.