The Role of NRAMP1/SLC11A1 Gene Variant D543N (1730G/A) in the Genetic Susceptibility to Develop Rheumatoid Arthritis in the Mexican Mestizo population.

Abstract

Rheumatoid arthritis is a chronic inflammatory disease whose cause has not been fully elucidated. However, genetic factors seem to have an important role in its pathogenesis. We analyzed the possible association between rheumatoid arthritis and variants of the SLC11A1 gene, which encodes for NRAMP1, a protein involved in the activation of phagocytes and synthesis of proinflammatory cytokines. In a case-control study in a Mexican Mestizo population, blood samples from 188 patients with rheumatoid arthritis and 133 healthy individuals were obtained to determine the frequency of SLC11A1 gene variants INT4 (469+14G/C or rs3731865), D543N (1730G/A or rs17235409) and 3'UTR (1729+55del4 or rs17235416) by polymerase chain reaction and restriction fragment length polymorphism. We found similar frequencies of INT4 and 3'UTR polymorphisms in patients and controls (p = 0.18 and 0.89, respectively). In contrast, a significantly lower frequency of the D543N polymorphism was observed in patients with rheumatoid arthritis compared to controls (p corrected = 0.016; OR: 0.48; 95% CI: 0.28-0.80). Our data suggest that the D543N variant of SLC11A1 gene has a protective effect in the development of rheumatoid arthritis, an interesting finding that has not been previously reported in any population.