Study reported in Nature Genetics found variants in potassium channel protein.

An international group of researchers have identified a potential new genetic target for the treatment of lone atrial fibrillation (AF), a form of AF that occurs in people with no other known cardiovascular disorders. They discovered that variants in the gene for the potassium channel protein KCNN3 were linked with the disorder in patients who developed the condition before 66 years of age and who had no history of heart failure.

The results are published in Nature Genetics in a paper titled “Common variants in KCNN3 are associated with lone atrial fibrillation.”

The study, led by Patrick Ellinor, M.D., Ph.D., at the Massachusetts General Hospital Cardiovascular Research Center and Cardiac Arrhythmia Service, involved a meta-analysis of genome-wide association studies involving 1,335 individuals with lone AF and 12,844 unaffected controls. The results highlighted variants at the 1q21 locus cluster at KCNN3 (also known as SK3 and KCa2.3), a gene coding for a voltage-independent calcium-activated potassium channel.

Proteins in this family are expressed in a number of excitable tissues including the brain and heart, the authors note. The researchers then confirmed their findings through data from two separate genome-wide association studies involving another 1,000 lone AF patients and 3,500 controls. 

“The genetic location we have identified could be a new drug target for the treatment of AF,” Dr. Ellinor suggests. “We are also investigating whether these variants can help us predict patients’ clinical outcomes or their response to the various treatments for AF.”

The authors add that further studies will be required to determine the mechanistic links between genetic variation at this locus and AF. They also point out that the observed associations don’t necessarily imply that the KCNN3 gene is directly involved in the pathogenesis of AF. “The associated SNPs may lie within or serve as proxies for noncoding regulatory elements that may affect gene expression at considerable distances from their respective genomic locations.” 

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