Why do certain hereditary diseases related to heart rhythm issues seem to affect women more than men? According to an experimental study out of Linköping University in Sweden, estrogen may play a key role. [1]
The study, published in Science Advances, determined that congenital diseases associated with arrhythmias such as Long QT syndrome result from mutations that affect the ion channels responsible for regulating the heart’s electrical activity. If higher levels of estrogen also negatively impact ion channel function in patients with these diseases, it could explain why women see more severe symptoms.
“We’re trying to understand which substances in the body impact the function of the ion channels. If we could figure out how this regulation works, maybe we can understand why some individuals are more protected and others are hit harder,” Sara Liin, an associate professor in the Department of Biomedical and Clinical Sciences at Linköping University, said in a statement about the study.
The research group was able to insert a human version of the ion channel Kv7.1/KCNE1—a channel frequently mutated in patients with LQTS—into frogs’ eggs. Then, they added estradiol—the most active form of estrogen—into those eggs. Their observations showed that the addition of estradiol indeed resulted in worse functioning of the ion channel. Other sex hormones, including progesterone, testosterone and two other forms of estrogen (estrone and estriol), had no effect.
The study also examined the range of ion channel mutations, noting that some appear to lead to high estrogen sensitivity while others appear to eliminate estrogen sensitivity altogether.
“We show that some hereditary mutations that reduce ion channel function seem to contribute to high estrogen sensitivity, so there could be two risk factors that interact especially in women carriers of these mutations," Lin said in the same statement. "We believe that our study gives good reason to look closer at this in patients."
View the full study here.