A variant in the endothelial nitric oxide synathase gene (eNOS) is associated with extra-articular manifestations of rheumatoid arthritis (RA) such as nodules, amyloidosis, and vasculitis, say researchers.
The finding is reported by Brazilian scientists in the journal Clinical Rheumatology and is based on a case–control study involving 105 consecutive RA patients and 100 healthy controls matched for geographic location and ethnicity.
All participants were genotyped for common eNOS polymorphisms, revealing that extra-articular manifestations were significantly greater among those who were C/C homozygotes for the T786C polymorphism than those with other genotypes.
Compared with heterozygotes and T/T homozygotes, individuals homozygous for the C/C genotype were 4.9 times more likely to exhibit extra-articular manifestations of RA, such as rheumatoid nodules, amyloidosis, vasculitis, pneumonitis, and episcleritisa. This is a statistically significant result, report Ricardo Machado Xavier (Federal University of Rio Grande do Sul in Porto Alegre) and team.
The allele and genotype frequencies of eNOS polymorphisms did not differ between cases and controls, however, suggesting that eNOS does not play a major role in susceptibility for RA.
Furthermore, there were no correlations between eNOS genotype and patient demographics, age at disease onset, age at diagnosis, rheumatoid factor positivity, erosions, or atlantoaxial subluxation.
Xavier and co-authors note that the T786C mutation in eNOS leads to reduced endothelial NO synthesis, which might perpetrate and augment the inflammatory cascade.
“Particularly in RA, [reduced NO synthesis] could predispose to a more severe disease with further influx of polymorphonuclear cells and release of inflammatory mediators, leading to cartilage destruction and subsequent bone erosions,” they conclude.
“Further studies are needed to confirm this association and elucidate the role of this polymorphism in the pathogenesis of clinical manifestations and cardiovascular disease in RA.”