Abstract |
Background
Atrial Fibrilation (AF) is one of the most common heart arrythmias affecting over
1% of the general population and is responsible for 3% of the hospitalizations.
It’s incidence increases with age, affecting 12.9% of male over the age of 70.
The reported incidence of post cardiac surgery AF ranges from 5% to 60%.
Multiple factors have been shown to confer susceptibility to post operative atrial
fibrilation, including changes in the sympathetic tone, electrolyte abnormalities,
β-blocker interruption and oxidative stress. It is belived that patients prone to
develop AF exibit a specific electrophysiologic profile. Nevertheless, in 10-20%
of the cases the predisposing factor cannot be identified.
Recent studies introduce the idea of genetic predispotion for AF, derived from
the increased incidence of AF in populations with polymorphisms on ion
channel forming genes. In fact, the majority of the associations between AF
and gene polymorphisms, involve genes coding potassium channels and more
specifically, the Iks channels.
Cardiac Iks channels are formed by α-subunits, and their properties can be
regulated through the binding of a β-subunit. The KCNQ1 gene codes for the
α-subunit of the Iks channel and it was the first to be related to familial AF.
Mutations in the KCNQ1 gene have led to further studies on KCNE1 gene, as
a possible target for genetic predisposition to AF.
The KCNE1 gene forms the β-subunit of the potassium channel carrying the
cardiac Iks current. Cardiac Iks channels contribute to atrial repolarization in
the late phase of the action potential. Cardiac Iks channels are capable of
modulating the action potential duration and restitution properties of the atrial
tissue as part of their contribution in the slowly activating delayed rectifier
potassium current.
A nonsynonymous, single-nucleotide polymorphism (SNP) in the KCNE1 gene
(A to G substitution at position 112, rs1805127), leading to a glycine substitution
for serine at amino-acid position 38 (S38G), was previously associated with
increased AF incidence. Of note, the S38G variant in the KCNE1 gene reduces
Iks current density and prolongs the atrial action potential duration, whereas
familial AF-causing
mutations in Iks channel genes have all had gain-of function effects.
In the present study, we assessed the impact of the KNCE1 S38G
polymorphism on the incidence of postoperative AF in a prospectively recruited
cohort of patients subjected to cardiac surgery. To the best of our knowledge,
no data are available on the effect of the KCNE1 polymorphisms to
postoperative AF.
Methods and results
A cohort of patients scheduled to undergo open heart surgery was prospectively
recruited. Blood samples were drawn and patient were followed for
development of AF post operatively until discharge. Genetic analysis was
performed using PCR, Sequencing and Restriction Fragment Length
Polymporphysm (RFLP). In toatl 509 patients were recruited of whom 203
(39.9%) had at least one qualifying episode of post operative AF.
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