Title : Lymphotoxin-alpha 252 A>G polymorphism: a link between disease susceptibility and dyslipidemia in rheumatoid arthritis? |
Abstract : OBJECTIVE: Rheumatoid arthritis (RA) is associated with higher levels of inflammatory mediators and with a more atherogenic lipid profile. Dyslipidemia can be present years before arthritis develops. Lymphotoxin-alpha (LTA) is a cytokine that mediates proinflammatory responses while also participating in lipid homeostasis, and its transcriptional activity is in part genetically determined. We examined the role of the single-nucleotide polymorphism at position 252 of the LTA gene in the genetic background of RA and dyslipidemia. METHODS: The association between the LTA 252 A>G polymorphism and disease status was examined in a nested case-control study of 388 patients with RA and 269 unrelated healthy controls, all white. Demographics and disease features were assessed, fasting lipids measured, and the use of lipid-lowering agents evaluated. RESULTS: The LTA 252 A allele was more frequent in cases compared to controls (70.5% and 64.3%, respectively; p = 0.018, OR 1.325, 95% CI 1.049-1.675), as well as the A/A genotype (50.8% vs 43.5%; p = 0.025). The A/A genotype was independently associated with dyslipidemia in patients, but not in controls. Patients with RA who had the LTA 252 G/G genotype were younger at disease onset and had higher C-reactive protein (CRP) levels. CONCLUSION: We found the LTA 252 A allele to be associated with an increased risk for developing RA in whites. The LTA 252 A/A genotype translates to a phenotype more prone to dyslipidemia, and the G/G genotype to a phenotype with earlier onset of disease and higher levels of CRP, when RA does occur. These observations highlight a possible common genetic predisposition to RA and dyslipidemia. |
Author : Santos MJ,Fernandes D,Caetano-Lopes J,Perpetuo IP,Vidal B,Canhao H,Fonseca JE, |
Source : J Rheumatol. 2011 Jul;38(7):1244-9. doi: 10.3899/jrheum.101170. Epub 2011 Apr 1. |