Help
Subscribe


All of GastroHep is now free access! - Click here to register Read For FREE - Our full range of review articles
GastroHep.com - the global online resource for all aspects of gastroenterology, hepatology and endoscopy
GastroHep.com - the global online resource for all aspects of gastroenterology, hepatology and endoscopy Profile of Guido Tytgat Profile of Pete Peterson Profile of Peter Cotton Profile of Roy Pounder

Home

News  
Journals
Review Articles
Slide Atlas
Video Clips
Online Books
Advanced Digestive Endoscopy
Classical Cases
Conference Diary
PubMed
International GH Links
USA GH Links
National GH Links
National GI Societies
Other Useful Links




Emails on Gastroenterology and Hepatology
the National AIDS Treatment Advocacy Project
Visit the gastroenterology section of the EUMS

News

Channelopathies in patients with irritable bowel syndrome

June's issue of Gastroenterology reports loss-of-function of the voltage-gated sodium channel NaV1.5 in patients with irritable bowel syndrome.

News image

SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5.

Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS).

Dr Michael Ackerman and colleagues from Minnesota, USA investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5.

The team performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS.

Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis.

A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls.

The research team found missense mutations in SCN5A in 2% of patients.

Missense mutations in SCN5A were found in 2% of patients
Gastroenterology

Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population.

However, the team noted that a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS than diarrhea-predominant IBS.

Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted NaV1.5 function.

The team observed that the The p. A997T-NaV1.5 had the greatest effect in reducing NaV1.5 function.

Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation normalized their bowel habits.

In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS.

Dr Ackerman and team commented, "About 2% of patients with IBS carry mutations in SCN5A."

"Most of these are loss-of-function mutations that disrupt NaV1.5 channel function."

"These findings provide a new pathogenic mechanism for IBS and possible treatment options."

Gastroenterol 2014: 146(7): 1659–1668
02 June 2014

Go to top of page Email this page Email this page to a colleague

 28 February 2015

Advanced search
 27 February 2015 
Obesity and weight-loss therapy
 27 February 2015 
MRE performance in staging liver fibrosis
 27 February 2015 
Bleeding in diverticulosis
 26 February 2015 
Familial colorectal cancer risk and primary cancer
 26 February 2015 
Questionnaires for GERD
 26 February 2015 
Herbal products and the liver
 25 February 2015 
Exercise and NAFLD
 25 February 2015 
IBD in Korea
 25 February 2015 
Immunosuppressive therapy and T. whipplei
 24 February 2015 
Clinical trials in pediatric IBD
 24 February 2015 
Reducing health care costs in IBD
 24 February 2015 
GI bleeding after anticoagulation interruption
 23 February 2015 
Visceral abdominal obesity and IBS
 23 February 2015 
Crohn's outcomes with infliximab
 23 February 2015 
Intestinal microbiota and celiac disease
 20 February 2015 
H. pylori eradication
 20 February 2015 
Antiviral treatment and Hep C outcomes
 20 February 2015 
C. diff testing in IBD
 19 February 2015 
Intestinal microbiota in IBS
 19 February 2015 
Peptic ulcer bleeding mortality in liver disease
 19 February 2015 
Fecal microbial transplant in active Crohn's disease
 18 February 2015 
Genetic testing and GI cancers
 18 February 2015 
Placebo analgesia in functional abdominal pain
 18 February 2015 
Successful Hep C virus therapy
 17 February 2015 
Quality measures and colonoscopist selection
 17 February 2015 
Global incidence of esophageal cancer
 17 February 2015 
Anti-viral treatment and survival in Hep C
 16 February 2015 
Saliva for the diagnosis of GERD
 16 February 2015 
H pylori eradication therapy
 16 February 2015 
Medical marijuana for digestive disorders
 13 February 2015 
Beta-blockers in cirrhosis
 13 February 2015 
Liver disease and peptic ulcer bleeding
 13 February 2015 
Prevalence of microscopic colitis
 12 February 2015 
Liver disease in chronic Hep C
 12 February 2015 
Patient-reported outcomes in Hep C
 12 February 2015 
Patients’ colonoscopist selection
 11 February 2015 
NAFLD and CVD
 11 February 2015 
Guidelines for the diagnosis of hepatocellular carcinoma
 11 February 2015 
Hepatic decompensation in Hep C cirrhosis
 10 February 2015 
Percutaneous endoscopic gastrostomy
 10 February 2015 
Factors that influence hepatic steatosis
 10 February 2015 
Gene variants and Crohn's susceptibility
 09 February 2015 
Factors that influence gallstone surgery
 09 February 2015 
Factors associated with increased mortality in cirrhosis
 09 February 2015 
Use of immunomodulators in IBD
 06 February 2015 
Colorectal cancer risk in IBD
 06 February 2015 
H. pylori and peptic ulcer bleeding
 06 February 2015 
IBS and somatization
 05 February 2015 
GERD, dyspepsia and IBS symptoms
 05 February 2015 
Quality of life in Crohn's after antitumor necrosis factor agents
 05 February 2015 
Thalidomide and refractory Crohn's
 04 February 2015 
Telemedicine in IBD
 04 February 2015 
Infliximab and muscle wasting in Crohn's
 04 February 2015 
Resistance mutations in chronic Hep B
 03 February 2015 
Testosterone in advanced liver disease
 03 February 2015 
Mortality in peptic ulcer bleeding
 03 February 2015 
Colonoscopic remission of ulcerative colitis
 02 February 2015 
Colonoscopy and colon cancer risk in IBD
 02 February 2015 
Sirolimus in Hep C virus infected liver graft recipients
 02 February 2015 
Treatment of C. diff in adults

Blackwell Publishing


GastroHep.com is a Blackwell Publishing registered trademark
© 2015 Wiley-Blackwell and GastroHep.com and contributors
Privacy Statement
Disclaimer
About Us