Referenced in: none

Automatically associated channels: Nav1.5

Title: SIDS: genetic and environmental influences may cause arrhythmia in this silent killer.

Authors: Jonathan C Makielski

Journal, date & volume: J. Clin. Invest., 2006 Feb , 116, 297-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16453014

Abstract
In this issue of the JCI, Bowers et al. show that the common polymorphism of the cardiac voltage-gated sodium channel, type Valpha (SCN5A), designated S1103Y, found in African Americans is associated with an increased risk of sudden infant death syndrome (SIDS). Wild-type and mutant SCN5A channels both functioned typically under normal conditions in vitro, but exposure to acidic intracellular pH levels such as those found in respiratory acidosis--a known risk factor for SIDS--produced abnormal gain-of-function late reopenings of S1103Y channels, behavior that is often associated with cardiac arrhythmias. These pathologic late reopenings were suppressed by low levels of the channel-blocking drug mexiletine. These findings provide an excellent illustration of a causal relationship between the interaction of the environment and genetic background in SIDS and also raise interesting questions about the linkage of a genetic abnormality with a clinical phenotype.