Public Release: 

Heart disease among some Japanese may be due to sequencing variation inside a gene

Findings may lead researchers to think 'inside the box' of nucleotide variation in the coding region to better understand ethnic difference in disease

American Physiological Society

April 9, 2003 (San Diego, CA) -- Previously published epidemiological studies have shown that there are ethnic differences in the prevalence of certain arrhythmogenic (heart-related) diseases. More recent reports indicate that mutations of the human gene SCN5A are linked to heart diseases, such as long QT syndrome type 3 (LQT3) and Brugada syndrome (BS). In a new study being presented today, researchers are suggesting that the sequencing variability inside a disease gene may also play a role in pinpointing heart disease among some ethnic groups.

A New Study
The authors of "A Collection of Nucleotide Variations in SCN5A, A Major Arrhythmogenic Gene, Among the Japanese," are Junko Masuda, George Koike, Hitoshi Kamiunten, and Akira Takeshita, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. Dr. Koike will present their findings on behalf of his colleagues during the American Physiology Society (APS) conference, Experimental Biology 2003, being held April 11-15, at the San Diego Convention Center, San Diego, CA.

Methodology
The SCN5A gene (sodium channel, voltage-gated, type V, alpha polypeptide) is responsible for the initial upstroke of the heart's action potential. Mutations of the gene cause a wide variety of arrhythmias, including LQT3, BS, idiopathic ventricular fibrillation and conduction disorder.

During the search for variation in SCN5A, some patients enrolled in a Japanese study were selected for further review: (1) two unrelated long QT syndrome type-3 patients; (2) two unrelated Brugada syndrome patients; and (3) two healthy subjects. Researchers prepared genomic DNA from the blood samples taken from the study subject. All exons covering entire coding region and exon-intron boundaries of SCN5A gene were amplified using PCR technology, and followed by direct sequencing analysis.

Results
The results showed that there were no nucleotide variations that result in amino acid substitution, and were unlikely to affect splicing. The research team considered that the diseases could be caused without any changes in the primary structure among the patients. In fact, the team was able to identify 13 novel nucleotide variations in the coding region and one in the exon-intron boundaries in a comparison to the National Center for Biotechnology Information (NCBI) sequence database.

Conclusions
This study strongly demonstrates that it is important to characterize sequence variations of any disease genes, since there are ethnic differences in sequence variations among genes. Utilizing this approach can lead to better understanding of ethnic differences in the genetic pathogenesis of human disease.

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The American Physiological Society (APS) is one of the world's most prestigious organizations for physiological scientists. These researchers specialize in understanding the processes and functions underlying human health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.

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