UH researchers investigate gene-environment interactions on the origins of two Guamanian neurodegenerative disorders

Disorders linked to low levels of essential minerals

University of Hawaiʻi
Meredith Hermosura, (808) 956-5212
UH Pacific Biosciences Research Center
Ralph Garruto, (607) 777-6562
State University of New York at Binghamton
Posted: Jul 29, 2005

HONOLULU — A team of University of Hawaiʻi researchers, along with collaborators from various institutes, have found a genetic variant of an ion channel in two distinct but related Guamanian neurodegenerative disorders, amyotrophic lateral sclerosis (ALS-G) and Parkinsonism dementia complex (PD-G). Their recent findings are reported in the July 28 online edition of the Proceedings in National Academy of Sciences.

The study is an attempt to understand the high incidence of ALS-G and PD-G in the islands of Guam and Rota in the Western Pacific fifty years ago. Cases of both disorders tended to cluster in areas characterized by very low levels of calcium and magnesium in soil and drinking water.

Incidence of ALS-G and PD-G has reduced in recent years due to modernization of the times that brought dietary changes and a treated water supply system to the affected villages. "The question remains, however, as to why only certain people eventually develop these diseases," said Meredith C. Hermosura of the UH Pacific Biosciences Research Center, and lead investigator of the study. "Our study is an initial attempt to understand this complex question."

The ion channel, TRPM7, is believed to be involved in regulating the levels of calcium and magnesium in cells, which led to question if there is a genetic variant of the channel that can be linked to the diseases. The genetic variant of TRPM7 found in ALS-G and PD-G causes a mutation in the ion channel that affects the channel‘s sensitivity to intracellular magnesium. Consequently, it could affect how the channel regulates intracellular calcium and magnesium levels. UH researchers and collaborators are currently engaged in studies to better understand the mechanisms involved.

Researchers who contributed to the study include: Dr. Hermosura and research associates at the Bekesy Laboratory of Neurobiology, Pacific Biosciences Research Center, University of Hawaiʻi; Maxim V. Dorovkov and Alexey G. Ryazanov of the Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey; David Haymer of the John A. Burns School of Medicine, University of Hawaiʻi; and Ralph Garruto, Laboratory of Biomedical Anthropology and Neurosciences, Binghamton University.

Garruto has worked extensively on ALS-G and PD-G and is a leading authority in the field. With colleague Richard Yanagihara (now at John A. Burns School of Medicine, University of Hawaiʻi) and others, he investigated the epidemiological connection between incidence of ALS-G and PD-G and an environment severely depleted in calcium and magnesium, providing the groundwork for this study.

This study was funded by a Collaborative Neuroscience Grant from the National Institute of Neurological Disorders and Stroke.

For more information on the study, visit http://www.pnas.org/cgi/content/abstract/0505149102v1.

About the Pacific Biosciences Research Center (PBRC)

The Pacific Biosciences Research Center (formerly known as the Pacific Biomedical Research Center) is a research institute of the University of Hawaiʻi system. Its mission is to encourage and foster research in diverse fields of biology. The pursuit of this goal is facilitated by a flexible organizational structure that is responsive to federal, state and university initiatives. The scientific approaches are as varied as the interests of the individual researchers and range from the molecular basis of biological function to large-scale ecological monitoring. PBRC researchers, most of whom are also affiliated with academic departments, provide training for graduate and undergraduate students, with a special emphasis on minority research opportunities.