SIDS: genetic and environmental influences may cause arrhythmia in this silent killer.
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.
Makielski
Jonathan C
JC
Department of Medicine, Cardiovascular Medicine Section and Department of Physiology, University of Wisconsin, Madison, Wisconsin 53792, USA. jcm@medicine.wisc.edu
D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D004777:Environment; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013398:Sudden Infant Death / Q000209:etiology / Q000235:genetics
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels