Role of C677T and A1298C MTHFR, A2756G MTR and -786 C/T eNOS gene polymorphisms in atrial fibrillation susceptibility.
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.
Giusti
Betti
B
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
Gori
Anna Maria
AM
Marcucci
Rossella
R
Sestini
Ilaria
I
Saracini
Claudia
C
Sticchi
Elena
E
Gensini
Francesca
F
Fatini
Cinzia
C
Abbate
Rosanna
R
Gensini
Gian Franco
GF
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
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase