Shana M Katzman1, Elsa S Strotmeyer2, Michael A Nalls3, Yiqiang Zhao4, Sean Mooney5, Nik Schork6, Anne B Newman2, Tamara B Harris7, Kristine Yaffe8, Steven R Cummings9, Yongmei Liu10, Gregory J Tranah11. 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.
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.
Authors: Alkes L Price; Gregory V Kryukov; Paul I W de Bakker; Shaun M Purcell; Jeff Staples; Lee-Jen Wei; Shamil R Sunyaev Journal: Am J Hum Genet Date: 2010-05-13 Impact factor: 11.025
Authors: Andreu Viader; Judith P Golden; Robert H Baloh; Robert E Schmidt; Daniel A Hunter; Jeffrey Milbrandt Journal: J Neurosci Date: 2011-07-13 Impact factor: 6.167
Authors: Tracy Stites; David Storms; Kathryn Bauerly; James Mah; Calliandra Harris; Andrea Fascetti; Quinton Rogers; Eskouhie Tchaparian; Michael Satre; Robert B Rucker Journal: J Nutr Date: 2006-02 Impact factor: 4.798
Authors: Anirban Maitra; Yoram Cohen; Susannah E D Gillespie; Elizabeth Mambo; Noriyoshi Fukushima; Mohammad O Hoque; Nila Shah; Michael Goggins; Joseph Califano; David Sidransky; Aravinda Chakravarti Journal: Genome Res Date: 2004-05 Impact factor: 9.043
Authors: Alex E Roher; Chera L Esh; Tyler A Kokjohn; Eduardo M Castaño; Gregory D Van Vickle; Walter M Kalback; R Lyle Patton; Dean C Luehrs; Ian D Daugs; Yu-Min Kuo; Mark R Emmerling; Holly Soares; Joseph F Quinn; Jeffrey Kaye; Donald J Connor; Nina B Silverberg; Charles H Adler; James D Seward; Thomas G Beach; Marwan N Sabbagh Journal: Alzheimers Dement Date: 2009-01 Impact factor: 21.566
Authors: L Santoro; F Manganelli; R Lanzillo; A Tessa; F Barbieri; F Pierelli; G Di Giacinto; V Nigro; F M Santorelli Journal: J Neurol Date: 2006-05-24 Impact factor: 4.849
Authors: Carlos A Vaz Fragoso; Todd M Manini; John A Kairalla; Thomas W Buford; Fang-Chi Hsu; Thomas M Gill; Stephen B Kritchevsky; Mary M McDermott; Jason L Sanders; Steven R Cummings; Gregory J Tranah Journal: Exp Gerontol Date: 2018-12-01 Impact factor: 4.032
Authors: Todd M Manini; Thomas W Buford; John A Kairalla; Mary M McDermott; Carlos A Vaz Fragoso; Roger A Fielding; Fang-Chi Hsu; Neil Johannsen; Stephen Kritchevsky; Tamara B Harris; Anne B Newman; Steven R Cummings; Abby C King; Marco Pahor; Adam J Santanasto; Gregory J Tranah Journal: Geroscience Date: 2018-10-18 Impact factor: 7.713
Authors: Thomas W Buford; Todd M Manini; John A Kairalla; Mary M McDermott; Carlos A Vaz Fragoso; Haiying Chen; Roger A Fielding; Abby C King; Anne B Newman; Gregory J Tranah Journal: J Am Heart Assoc Date: 2018-09-18 Impact factor: 5.501