New gene associated with increased risk of Alzheimer's disease
2010-09-24
(Press-News.org) Researchers have identified a gene that appears to increase a person's risk of developing late-onset Alzheimer disease (AD), the most common type of the disease. Abbreviated MTHFD1L, a gene on chromosome six, was identified in a genome-wide association study by a team of researchers led by Margaret Pericak-Vance, Ph.D., director of the John P. Hussman Institute for Human Genomics (HIHG) at the University of Miami Miller School of Medicine. Details appear September 23 in the open-access journal PLoS Genetics.
The World Health Organization estimates that there are currently 18 million people worldwide with Alzheimer's disease, and this figure is projected to nearly double to 34 million by 2025. By looking at gene variation throughout the human genomes of 2,269 subjects with late-onset AD and 3,107 without the disease, researchers were able to pinpoint small differences in the genetic sequences of people with and without AD.
The study found that individuals with a particular variation in the gene MTHFD1L may be almost twice as likely to develop AD as those people without the variation.
"We are hopeful our identification of MTHFD1L as a risk gene for Alzheimer's disease will help us to better understand how this disease develops and potentially serve as a marker for people who may be at increased risk," said co- author Adam Naj, Ph.D.
"Identifying this gene is important because the gene is known to be involved in influencing the body's levels of homocysteine, and high levels of homocysteine are a strong risk factor for late-onset Alzheimer's disease," said Dr. Pericak-Vance. "In addition, variations of the MTHFD1L gene have been reported to possibly increase the risk of coronary artery disease. Since the function of blood vessels in the brain may affect Alzheimer's disease, this finding may also help us understand how homocysteine levels and blood vessel function in the brain affect Alzheimer's disease."
"By applying the new tools of genomics we are now making rapid progress in finding out what genetic changes are involved in Alzheimer disease. These findings will lead to a better understanding of what's happening in Alzheimer disease, and how we can improve treatments," said Jonathan Haines, Ph.D., Principal Investigator at Vanderbilt University School of Medicine.
"This finding gives us unique insight into possible interactions between genetic and environmental risk factors that contribute to AD," said Joseph Buxbaum, Ph.D., from Mount Sinai School of Medicine in New York and a co-author of the study. "We know of environmental and lifestyle factors that can impact homocysteine levels and it will be important to understand whether variations of the MTHFD1L gene can modulate these effects."
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FINANCIAL DISCLOSURE: This work was supported by the National Institutes of Health National Institute on Aging (grants AG027944, AG20135, AG19757, AG010491, AG002219, and AG005138) and the National Institute of Neurological Disorders and Stroke (grants NS31153 and NS039764), the Alzheimer's Association, and the Louis D. Scientific Award of the Institut de France. JDB is the G. Harold and Leila Y. Mathers Professor of Geriatrics and Adult Development. Samples from the National Cell Repository for Alzheimer's Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
CITATION: Naj AC, Beecham GW, Martin ER, Gallins PJ, Powell EH, et al. (2010) Dementia Revealed: Novel Chromosome 6 Locus for Late-Onset Alzheimer Disease Provides Genetic Evidence for Folate-Pathway Abnormalities. PLoS Genet 6(9): e1001130. doi:10.1371/journal.pgen.1001130
PLEASE ADD THIS LINK TO THE FREELY AVAILABLE ARTICLE IN ONLINE VERSIONS OF YOUR REPORT (the link will go live when the embargo ends): http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001130
PRESS-ONLY PREVIEW OF THE ARTICLE:
http://www.plos.org/press/plge-06-09-pericakvance.pdf
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[Press-News.org] New gene associated with increased risk of Alzheimer's disease
