C677T and A1298C MTHFR, A2756G MTR and 844ins68 CBS Gene Polymorphisms in Atrial Fibrillation

Abstract number: P1124

Giusti¹ B, Gensini² F, Sestini¹ I, Lenti¹ M, Saracini¹ C, Falciani¹ M, Innocenti¹ D, Pepe¹ G, Abbate¹ R, Gensini¹ GF

¹¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ¹¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ²²Department of Clinical Pathophysiology, Unit of Medical Genetics, University of Florence, Italy

Elevated plasma total homocysteine (tHcy) concentrations are a risk factor for cerebrovascular disease. Recent data indicate that hyperhomocysteinemia is a risk factor for atrial fibrillation (AF). Hyperhomocysteinemia may be associated with the presence of polymorphisms in genes codifying for enzymes involved in the Hcy metabolism. Aim of this study was to evaluate the prevalence of C677T and A1298C of 5, 10-methylenetetrahydrofolate reductase (MTHFR), A2756G of methionine synthase (MTR) and 844ins68 of cystathionine b synthase (CBS) gene polymorphisms in relation to homocysteine (Hcy) in AF patients. We studied 245 patients with AF and 245 matched healthy control subjects. For polymorphism detection, DNA was amplified by PCR and genotype was determined by microarray technology by using electronic chips (Nanogen technology). Hcy plasma levels were significantly higher in AF patients than in controls (14.8, 5.4–54.1 versus 11.5, 1.6–52.6 umol/L, P= 0.001). Hcy plasma levels were significantly higher in AF patients with history of ischemic event(s) than in AF patients without history (15.4, 5.4–54.1 versus 13.9, 6.7–38.6 µmol/L, P < 0.05). The prevalence of homozygous C677T genotype was similar in AF patients (17.7%) in comparison to controls (18.3%); the prevalence of homozygous C677T genotype was significantly (P < 0.05) higher in patients with ischemic events (24.4%) than in those (9.9%) without events. No difference in the prevalence of homozygotes for all the other polymorphisms investigated in AF patients and controls was observed. The risk of AF significantly increased in the higher quartile of Hcy (OR = 4.50, 95% CI 2.73–7.44). The highest Hcy quartile and C677T homozygosity were associated with an increased risk of ischemic events (Hcy OR = 2.62, 95% CI 1.40–4.92; C677T OR = 2.95, 95% CI 1.53–5.67). In conclusion, our results confirm an association between elevated tHcy levels and the presence of AF and cerebrovascular events. Among the polymorphisms involved in methionine metabolism, MTHFR C677T polymorphism, but not MTHFR A1298C, MTR A2756G and CBS 844ins68 polymorphisms was associated with the occurrence of cerebrovascular events in AF patients.