Published: 21-03-2014 09:32 | Updated: 21-03-2014 09:32

New study links irritable bowel syndrome to defective gene and heart disease

An international study, including researchers from Karolinska Institutet, reveals potential new pathogenetic mechanism for irritable bowel syndrome (IBS), which involves functional defects in the voltage-gated sodium channel NaV1.5 in the gastrointestinal smooth muscle and pacemaker cells.

Approximately 15 to 20 percent of the Western world has IBS. It is a common disorder that affects the large intestine. Most patients with the disorder commonly experience symptoms of cramping, abdominal pain, diarrhea and constipation.

Previous investigations had found that a considerable number of patients with cardiac arrhythmias and mutations in SCN5A (the gene for NaV1.5) also had gastrointestinal symptoms. In the present study, research teams at Mayo Clinic Rochester, USA sequenced DNA from more than 500 IBS patients and identified SCN5A mutations in approximately 2 percent of them. This finding was further supported by work coordinated by Mauro D’Amato of Karolinska Institutet through genome-wide association studies and replication analyses of four independent cohorts of 1,715 IBS patients and controls.

In addition, researchers at Mayo Clinic focused on one IBS patient with severe constipation, and were able to normalize bowel habits through the administration of mexiletine – a drug used to treat cardiac arrhythmias – which can restore sodium current in cells expressing mutant SCN5A. These results build on research in IBS suggesting that components of this disorder have a genetic background, and open up for novel therapeutic approaches in 2 percent suspected IBS patients that may have abnormally functioning NaV1.5.

Mayo Clinic News Network


Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome.
Beyder A, Mazzone A, Strege P, Tester D, Saito Y, Bernard C, et al
Gastroenterology 2014 Jun;146(7):1659-1668