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J Gerontol A Biol Sci Med Sci. 2015 Nov;70(11):1400-8. doi: 10.1093/gerona/glu175. Epub 2014 Nov 13.

Mitochondrial DNA Sequence Variation Associated With Peripheral Nerve Function in the Elderly.

Author information

1
Department of Innovation, Technology, and Alliances, University of California, San Francisco and.
2
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania and.
3
Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, Maryland and.
4
State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing, China and.
5
Department of Bioinformatics, Buck Institute for Research on Aging, Novato, California and.
6
Department of Human Biology, J. Craig Venter Institute, La Jolla, California and.
7
Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland and.
8
Departments of Psychiatry, Neurology, and Epidemiology, University of California, and Department of Geriatric Psychiatry, San Francisco VA Medical Center and.
9
California Pacific Medical Center Research Institute, San Francisco and.
10
Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
11
California Pacific Medical Center Research Institute, San Francisco and gtranah@sfcc-cpmc.edu.

Abstract

BACKGROUND:

Mitochondrial dysfunction is a prominent hallmark of many sensory neuropathies. The purpose of this study was to assess the influence of mitochondrial DNA sequence variation on peripheral nerve function in the population-based Health, Aging, and Body Composition Study.

METHODS:

We investigated the role of common mitochondrial DNA variation (n = 1,580) and complete mitochondrial DNA sequences (n = 138) on peroneal motor nerve conduction velocity and amplitude, average vibration detection threshold, and monofilament sensitivity.

RESULTS:

Nominal associations among common mitochondrial DNA variants and haplogroups were identified but were not statistically significant after adjustment for multiple comparisons. Sequence-based approaches were used to identify aggregate variant associations across the 16S rRNA (weighted-sum, p = 2E-05 and variable threshold, p = 9E-06) for nerve conduction velocity. Several of these rare 16S variants occurred at or near sites with earlier disease associations and are also in close proximity to the peptidyl transferase center, which is the catalytic center of the 16S rRNA CONCLUSIONS: These results suggest that sequence variation related to mitochondrial protein synthesis/assembly is associated with peripheral nerve function and may provide insight into targets for intervention or new clinical strategies to preserve nerve function in late life.

KEYWORDS:

Epidemiology; Functional Performance.; Genetics; Sensory

PMID:
25394619
PMCID:
PMC4612380
DOI:
10.1093/gerona/glu175
[Indexed for MEDLINE]
Free PMC Article

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