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AAN: New Gene Associated With Alzheimer’s Disease

Last Updated: April 14, 2010.

 

Study suggests that variation in MTHFD1L is linked to increased risk of late-onset disease

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Variation in MTHFD1L -- a gene involved in mitochondrial tetrahydrofolate synthesis associated with risk of neural tube defects and mRNA splicing efficiency -- may be a novel risk factor for late-onset Alzheimer's disease, according to research presented at the annual meeting of the American Academy of Neurology, held from April 10 to 17 in Toronto.

WEDNESDAY, April 14 (HealthDay News) -- Variation in MTHFD1L -- a gene involved in mitochondrial tetrahydrofolate synthesis associated with risk of neural tube defects and mRNA splicing efficiency -- may be a novel risk factor for late-onset Alzheimer's disease, according to research presented at the annual meeting of the American Academy of Neurology, held from April 10 to 17 in Toronto.

Margaret Pericak-Vance, Ph.D., of the University of Miami Miller School of Medicine's John P. Hussman Institute for Human Genomics, and colleagues combined data on 483,399 single nucleotide polymorphisms from a previously reported genome-wide association study of 492 late-onset Alzheimer's disease cases and 496 controls, and from a novel set of 439 late-onset Alzheimer's disease cases and 608 cognitive controls. Associations exceeding the experiment-wide significance threshold were replicated in an additional 1,338 cases and 2,003 controls.

The researchers found that the single nucleotide polymorphism rs11754661 at 151.2Mb of chromosome 6q25.1 in the gene MTHFD1L was significantly associated with late-onset Alzheimer's disease. In addition, subsequent genotyping of single nucleotide polymorphisms in high linkage disequilibrium with rs11754661 identified statistically significant associations in multiple single nucleotide polymorphisms (rs803424, rs2073067, and rs2072064).

"This finding is noteworthy for late-onset Alzheimer's disease pathology specifically, as MTHFD1L may play a role in the generation of methionine from homocysteine and influence homocysteine-related pathways," the authors conclude. "Levels of homocysteine are a known risk factor for late-onset Alzheimer's disease development. Also, variation in MTHFD1L has been previously reported in a genome-wide association study to have a statistically significant association with coronary artery disease risk, which may suggest a role in vascular features of Alzheimer's disease."

One co-author disclosed financial ties to Athema Diagnostics; another co-author disclosed financial ties to Sabine Neurotechnology.

Abstract No. P03.296
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Copyright © 2010 HealthDay. All rights reserved.


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