Analysis of minK and eNOS genes as candidate loci for predisposition to non-valvular atrial fibrillation.
OBJECTIVE
Mink protein, a beta-subunit of I(ks) potassium channels modulate cardiac cellular electrophysiology, and experimental data demonstrated that NO is involved in cardiac vagal activity and in the inhibition of sympathetic activity. We evaluated the role of eNOS -786T>C, 894G>T, 4a/4b and of minK S38G polymorphisms as predisposing factors to non-valvular atrial fibrillation (NVAF).


RESULTS
We studied 331 consecutive patients with documented NVAF and in 441 control subjects, comparable for age and gender. A significant difference in allele frequencies between patients and controls for minK S38G and eNOS -786T>C, but not for eNOS 894G>T and 4a/4b polymorphisms, was observed. The minK 38G allele was significantly associated with susceptibility to NVAF at both univariate and multivariable analysis, according to dominant and recessive genetic model (multivariable analysis, dominant: OR=1.73, P=0.004 and recessive: OR=1.59, P=0.006). The eNOS -786C allele weakly influenced NVAF at univariate analysis, according to the dominant model (OR=1.50, P=0.01). The contemporary presence of minK 38G and eNOS -786C alleles increased the predisposition to NVAF, after adjustment with cardiovascular risk factors (OR minK 38G*eNOS -786C=2.11, P<0.0001; OR=2.58, P=0.003; OR=3.08, P=0.002, according to dominant, recessive, and additive model, respectively).


CONCLUSIONS
Our findings suggest a role for minK and eNOS genes as predisposing factors to NVAF.
Fatini
Cinzia
C
Department of Medical and Surgical Critical Care; Thrombosis Centre, Azienda Ospedaliero-Universitaria, University of Florence, Viale Morgagni 85, 50134, Italy. cinziafatini@hotmail.com
Sticchi
Elena
E
Genuardi
Maurizio
M
Sofi
Francesco
F
Gensini
Francesca
F
Gori
Anna Maria
AM
Lenti
Meri
M
Michelucci
Antonio
A
Abbate
Rosanna
R
Gensini
Gian Franco
GF
D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*
C489622:KCNE1 protein, human; D024642:Potassium Channels, Voltage-Gated; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III