Previous studies have indicated that mutations within the SCN5A gene are linked to development of arrhythmogenic cardiac disorders. Sequence variability within such a gene may play a role in differences in prevalence seen among ethnic groups, according to a presentation at the American Physiology Society-sponsored conference, Experimental Biology 2003.

Junko Masuda, M.D., and his Japanese colleagues studied the SCN5A gene (sodium channel, voltage-gated, type 5, alpha polypeptide), which is responsible for the initial upstroke of the action potential. Mutations are known to cause a wide variety of arrhythmias, including long QT syndrome type 3, Brugada syndrome, idiopathic ventricular fibrillation, and conduction disorder.

During the search for different mutations, some patients enrolled in a Japanese study were selected for further review: 2 unrelated people with long QT syndrome type 3, 2 unrelated people with Brugada syndrome, and 2 healthy subjects. Researchers prepared genomic DNA from blood samples. All exons covering the entire coding region and exon-intron boundaries of the SCN5A gene were amplified with use of polymerase chain reaction technology and followed by direct sequencing analysis.

Investigators found there were no nucleotide variations that resulted in amino acid substitution and none that were likely to affect splicing. The research team considered the possibility that the diseases could be caused without any changes in primary protein structure.

The team was able to identify 13 novel nucleotide variations in the coding region and 1 in the exon-intron boundaries in comparison with data in the National Center for Biotechnology Information database.

The researchers concluded that such sequence variation analysis within a known disease-causing gene may lead to better understanding of ethnic differences in the genetic pathogenesis of a single disease.