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
- myocardial infarction
- rheumatoid arthritis