Gastrointestinal symptoms in families of patients with an SCN5A-encoded cardiac channelopathy: evidence of an intestinal channelopathy

Am J Gastroenterol. 2006 Jun;101(6):1299-304. doi: 10.1111/j.1572-0241.2006.00507.x.


Objectives: Recently, two ion channels associated with congenital long QT syndrome, the SCN5A-encoded Nav1.5 sodium channel and the KCNH2-encoded HERG potassium channel (IKr), have been found on gastrointestinal smooth muscle and interstitial cells of Cajal. The aim of this study was to determine if the cardiac channelopathy-associated mutations in SCN5A or KCNH2 are associated with GI symptom complexes.

Methods: Mayo Clinic's Sudden Death Genomics Laboratory performed comprehensive mutational analysis on index patients referred for long QT syndrome genetic testing and their family members thus establishing a cohort of families for which the genotype status for SCN5A or KCNH2 is known. A valid GI symptom questionnaire was mailed to all family members (both genotype positive and genotype negative) in this cohort. The association between cardiac channel genotype and GI symptoms was assessed by logistic regression adjusted for age and sex.

Results: Two hundred and nineteen (43% of 529) subjects returned the questionnaire. Fifty percent of the subjects with an SCN5A mutation reported abdominal pain compared to only 13% of controls (OR 5.7; 95% CI 1.3-24.4). Over 65% of subjects with an SCN5A mutation reported a GI symptom complex compared to 28% of controls (OR 5.2; 95% CI 1.5-18.3). No associations with KCNH2 genotype status were detected.

Conclusions: This study is the first to suggest an association between a well-defined cardiac channelopathy and GI symptoms. The role of sodium channelopathies in the pathogenesis of digestive diseases merits exploration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Gastrointestinal Diseases / genetics*
  • Genotype
  • Humans
  • Infant
  • KCNQ Potassium Channels / genetics*
  • Logistic Models
  • Long QT Syndrome / congenital
  • Long QT Syndrome / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Sodium Channels / genetics*
  • Surveys and Questionnaires


  • KCNQ Potassium Channels
  • Sodium Channels