HOME > About Nagasaki University > Research information > Paper Jointly Authored by Professor Naomasa Makita of the Graduate School of Biomedical Sciences Department of Physiology of Visceral Function and Body Fluid Published in Electronic Version of British Scientific Journal, "Nature Genetics"

Paper Jointly Authored by Professor Naomasa Makita of the Graduate School of Biomedical Sciences Department of Physiology of Visceral Function and Body Fluid Published in Electronic Version of British Scientific Journal, "Nature Genetics"

July 22, 2013

A research article titled "Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death" was published in the electronic version of the British science journal "Nature Genetics" (July 21, 6:00 p.m. BST, July 22, 2:00 a.m. JST).

Professor Naomasa Makita of Department of Molecular Physiology, Nagasaki University Graduate School of Biomedical Sciences engaged in joint international research with four sites in Japan and 14 in Europe and America, finding the gene responsible for Brugada syndrome, a genetic arrhythmia that predisposes affected individuals to sudden death.

In Japan, there have been many cases of otherwise healthy people being found dead by family members in the morning. These cases are frequently called "Pokkuri disease" in Japanese, meaning sudden unexpected death. Pathophysiology of Pokkuri disease is in fact attributable largely to Brugada syndrome. Identification of familial cases of Brugada syndrome strongly suggests some genetic predispositions underlying this potential lethal arrhythma. Extensive genetic studies over 20 years have revealed mutations gene SCN5A in about 20% cases, however, the genetic causes remain unknown in 80% cases.

The research group performed genome-wide association study (GWAS), comparing single nucleotide polymorphisms (SNPs) in the entire genome between Brugada syndrome cases and normal controls, and discovered two genetic regions associated Brugada syndrome; SCN10A and HEY2. Replicated study using two independent populations of 1,449 Caucasian and 1,224 Japanese (including 79 Brugada syndrome patients and 100 normal controls registered from Nagasaki University) confirmed that individuals carrying three SNPs located at the SCN10A and HEY2 have 20.4 times higher predisposition to Brugada syndrome than controls.

Generally, rare diseases are defined by a single genetic mutation, while the risk of common diseases is increased by accumulation of multiple factors. This research demonstrates that common genetic differences (polymorphism) can be strongly involved even in rare diseases such as Brugada syndrome.

Further international collaborations on genetic and molecular cell biology studies are underway to elucidate the pathophysiology underlying other heart diseases as well as Brugada syndrome.