AIM: 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). METHODS AND 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). CONCLUSION: Our findings suggest a role for minK and eNOS genes as predisposing factors to NVAF.
AIM: 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 minKS38G polymorphisms as predisposing factors to non-valvular atrial fibrillation (NVAF). METHODS AND 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 minKS38G 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). CONCLUSION: Our findings suggest a role for minK and eNOS genes as predisposing factors to NVAF.
Authors: Moritz F Sinner; Steven A Lubitz; Arne Pfeufer; Seiko Makino; Britt-Maria Beckmann; Kathryn L Lunetta; Gerhard Steinbeck; Siegfried Perz; Rosanna Rahman; Akshata Sonni; Steven M Greenberg; Karen L Furie; H-Erich Wichmann; Thomas Meitinger; Annette Peters; Emelia J Benjamin; Jonathan Rosand; Patrick T Ellinor; Stefan Kääb Journal: Heart Rhythm Date: 2010-11-04 Impact factor: 6.343
Authors: Saagar Mahida; Steven A Lubitz; Michiel Rienstra; David J Milan; Patrick T Ellinor Journal: Cardiovasc Res Date: 2010-11-30 Impact factor: 10.787