title: Lymphotoxin-α 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-α (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.
  
  
  CONCLUSIONS
  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.
authors: Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. mjps@netvisao.pt
authors: Maria J
authors: MJ
authors: Santos
authors: Diana
authors: D
authors: Fernandes
authors: Joana
authors: J
authors: Caetano-Lopes
authors: Inês P
authors: IP
authors: Perpetuo
authors: Bruno
authors: B
authors: Vidal
authors: Helena
authors: H
authors: Canhao
authors: João E
authors: JE
authors: Fonseca
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D050171:Dyslipidemias / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011174:Portugal; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D008055:Lipids; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein