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The Lymphotoxin 252A>G polymorphism is common and associates with Myocardial Infarction in patients with rheumatoid arthritis
  1. Vasileios F Panoulas (bpanoulas{at}hotmail.com)
  1. Russells Hall Hospital, Dudley Group of Hospitals, NHS Trust, United Kingdom
    1. Spyridon N Nikas (snnikas{at}yahoo.com)
    1. Russells Hall Hospital, Dudley Group of Hospitals, NHS Trust, United Kingdom
      1. Jacqueline P Smith (jacqueline.smith{at}dgoh.nhs.uk)
      1. Russells Hall Hospital, Dudley Group of Hospitals, NHS Trust, United Kingdom
        1. Karen M J Douglas (karen.douglas{at}dgoh.nhs.uk)
        1. Russells Hall Hospital, Dudley Group of Hospitals, NHS Trust, United Kingdom
          1. Peter Nightingale (peter.nightingale{at}uhb.nhs.uk)
          1. Wolfson Computer Laboratory - University Hospital Birmingham NHS Foundation Trust, United Kingdom
            1. Haralampos J Milionis (hmilioni{at}cc.uoi.gr)
            1. Department of Internal Medicine, University of Ioannina, Greece
              1. Gareth J Treharne (gjt884{at}bham.ac.uk)
              1. Russells Hall Hospital, Dudley Group of Hospitals, NHS Trust, United Kingdom
                1. Tracey E Toms (tracey.toms{at}dgoh.nhs.uk)
                1. Russells Hall Hospital, Dudley Group of Hospitals, NHS Trust, United Kingdom
                  1. Marina D Kita (yiola{at}otenet.gr)
                  1. Russells Hall Hospital, Dudley Group of Hospitals, NHS Trust, United Kingdom
                    1. George D Kitas (g.d.kitas{at}bham.ac.uk)
                    1. Russells Hall Hospital, Dudley Group of Hospitals, NHS Trust, United Kingdom

                      Abstract

                      Objective: Cardiovascular disease (CVD) is more prevalent and more likely to lead to death in patients with rheumatoid arthritis (RA). Single nucleotide polymorphisms (SNPs) of the genes for Lymphotoxin-A (LT-A) and its regulatory protein galectin-2 (LGALS2) have been implicated as genetic risk factors for acute cardiovascular events in the general population: we hypothesized that their risk alleles/genotypes (a) may be more frequent amongst RA patients compared to non-RA controls, explaining part of the increased CVD in RA; (b) may be more frequent amongst RA patients with prevalent CVD compared with RA patients without CVD.

                      Methods: Genomic DNA samples were collected from 388 RA patients and 399 local population controls without RA. LT-A gene intron 1 252A>G and LGALS2 intron 1 3279C>T SNPs were identified using real time PCR and melting curve analysis.

                      Results: LT-A 252GG homozygotes were significantly more prevalent among RA patients compared to controls (19.8 % vs. 11.8%, p=0.002; ORGG/GA,AA=1.85, 95% CI 1.25 to 2.75, p=0.002). RA patients possessing LT-A 252 GG were significantly more likely to have had a myocardial infarction (MI) compared to those with LT-A 252 AA or GA (13% vs. 5.5%, p=0.02; adjusted ORGG/GA,AA=3.03, 95% CI 1.2 to 7.68, p=0.002). The frequency of LGALS2 polymorphisms was similar between RA and controls and did not associate with CVD within RA patients.

                      Conclusions: The LT-A 252GG genotype occurs more frequently among patients with RA than the general population. In RA, this genotype appears to associate with increased likelihood of suffering an MI.

                      • cardiovascular disease
                      • gene
                      • lymphotoxin-alpha
                      • myocardial infarction
                      • rheumatoid arthritis

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