Mitochondrial DNA Sequence Variation Associated With Peripheral Nerve Function in the Elderly.
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.
Department of Innovation, Technology, and Alliances, University of California, San Francisco and.
Shana M
SM
Katzman
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania and.
Elsa S
ES
Strotmeyer
Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, Maryland and.
Michael A
MA
Nalls
State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing, China and.
Yiqiang
Y
Zhao
Department of Bioinformatics, Buck Institute for Research on Aging, Novato, California and.
Sean
S
Mooney
Department of Human Biology, J. Craig Venter Institute, La Jolla, California and.
Nik
N
Schork
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania and.
Anne B
AB
Newman
Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland and.
Tamara B
TB
Harris
Departments of Psychiatry, Neurology, and Epidemiology, University of California, and Department of Geriatric Psychiatry, San Francisco VA Medical Center and.
Kristine
K
Yaffe
California Pacific Medical Center Research Institute, San Francisco and.
Steven R
SR
Cummings
Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Yongmei
Y
Liu
California Pacific Medical Center Research Institute, San Francisco and gtranah@sfcc-cpmc.edu.
Gregory J
GJ
Tranah
D000368:Aged; D001823:Body Composition; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009431:Neural Conduction / Q000502:physiology*; D010543:Peroneal Nerve / Q000502:physiology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D011930:Reaction Time / Q000502:physiology
D004272:DNA, Mitochondrial; D012336:RNA, Ribosomal, 16S
Epidemiology; Functional Performance.; Genetics; Sensory