Cardiac arrhythmia and thyroid dysfunction: a novel genetic link

Int J Biochem Cell Biol. 2010 Nov;42(11):1767-70. doi: 10.1016/j.biocel.2010.07.013. Epub 2010 Aug 3.

Abstract

Inherited Long QT Syndrome (LQTS), a cardiac arrhythmia that predisposes to the often lethal ventricular fibrillation, is commonly linked to mutations in KCNQ1. The KCNQ1 voltage-gated K(+) channel α subunit passes ventricular myocyte K(+) current that helps bring a timely end to each heart-beat. KCNQ1, like many K(+) channel α subunits, is regulated by KCNE β subunits, inherited mutations in which also associate with LQTS. KCNQ1 and KCNE mutations are also associated with atrial fibrillation. It has long been known that thyroid status strongly influences cardiac function, and that thyroid dysfunction causes abnormal cardiac structure and rhythm. We recently discovered that KCNQ1 and KCNE2 form a thyroid-stimulating hormone-stimulated K(+) channel in the thyroid that is required for normal thyroid hormone biosynthesis. Here, we review this novel genetic link between cardiac and thyroid physiology and pathology, and its potential influence upon future therapeutic strategies in cardiac and thyroid disease.

Publication types

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

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / genetics*
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / physiopathology*
  • Atrial Fibrillation / genetics
  • Atrial Fibrillation / metabolism
  • Atrial Fibrillation / physiopathology
  • Humans
  • Hyperthyroidism / genetics
  • Hyperthyroidism / metabolism
  • Hyperthyroidism / physiopathology
  • Hypothyroidism / genetics
  • Hypothyroidism / metabolism
  • Hypothyroidism / physiopathology
  • KCNQ1 Potassium Channel / genetics
  • Long QT Syndrome / genetics
  • Long QT Syndrome / metabolism
  • Long QT Syndrome / physiopathology
  • Potassium Channels, Voltage-Gated / genetics
  • Thyroid Diseases / genetics*
  • Thyroid Diseases / metabolism
  • Thyroid Diseases / physiopathology*

Substances

  • KCNQ1 Potassium Channel
  • Potassium Channels, Voltage-Gated