title: Role of C677T and A1298C MTHFR, A2756G MTR and -786 C/T eNOS gene polymorphisms in atrial fibrillation susceptibility.
abstract: BACKGROUND
  Hyperhomocysteinemia has been suggested to play a role in the NonValvular Atrial Fibrillation (NVAF) pathogenesis. Polymorphisms in genes coding for homocysteine (Hcy) metabolism enzymes may be associated with hyperhomocysteinemia and NVAF.
  
  
  METHODS
  456 NVAF patients and 912 matched controls were genotyped by an electronic microchip technology for C677T and A1298C MTHFR, A2756G MTR, and -786C/T eNOS gene polymorphisms. Hcy was determined by an immunoassay method.
  
  
  RESULTS
  The genotype distribution of the four polymorphisms as well as genotype combinations did not differ in patients and controls. Hcy was higher in patients than in controls (15.2, 95%CI 14.7-15.7 vs 11.3, 95%CI 11.0-11.6 micromol/L; p<0.0001). In both populations, a genotype-phenotype association (p<0.0001) between Hcy and C677T MTHFR polymorphism was observed; in controls a significant (p = 0.029) association between tHcy and -786C/T eNOS polymorphism was also observed. At the multivariate analysis the NVAF risk significantly increased in the upper quartiles of Hcy compared to the lowest: OR from 2.8 (1.68-4.54 95%CI) in Q2 to 12.9 (7.96-21.06 95%CI) in Q4.
  
  
  CONCLUSIONS
  Our data demonstrated the four polymorphisms, although able, at least in part, to affect Hcy, were not associated with an increased risk of NVAF per se or in combination.
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, DENOTHE, University of Florence, Florence, Italy. betti.giusti@unifi.it
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Gori
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.forename: Ilaria
authors.initials: I
authors.lastname: Sestini
authors.forename: Claudia
authors.initials: C
authors.lastname: Saracini
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gensini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fatini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000097:blood / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase