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

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.

SUBMITTER: Katzman SM

PROVIDER: S-EPMC4612380 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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

Katzman Shana M SM Strotmeyer Elsa S ES Nalls Michael A MA Zhao Yiqiang Y Mooney Sean S Schork Nik N Newman Anne B AB Harris Tamara B TB Yaffe Kristine K Cummings Steven R SR Liu Yongmei Y Tranah Gregory J GJ

The journals of gerontology. Series A, Biological sciences and medical sciences 20141113 11

<h4>Background</h4>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.<h4>Methods</h4>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 vib ...[more]

PMID: 25394619

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Project description:Abstract Meningiomas are the most common primary central nervous system tumors. Risk factors include female sex, African American race, a higher body mass index, and exposure to ionizing radiation. Genome-wide association studies have identified two risk loci for meningioma in the nuclear genome (rs12770228 and rs2686876). Whereas mitochondrial DNA (mtDNA) sequence variants and haplogroups have been linked with certain cancers, research on meningioma is lacking. We examined the association of 42 common (minor allele frequency ≥ 5%) germline mtDNA variants, haplogroups, and genes with meningioma risk in 1,080 controls and 478 cases from a case-control study conducted at medical centers in the southeastern US. Participant DNA samples were genotyped using the UK Biobank array that included a set of common and rare mtDNA variants. Risk associations were examined separately for meningioma overall, WHO grade 1 (n=409) and WHO grade 2/3 (n=69) meningiomas. Overall, meningioma risk was significantly higher among women (OR=2.86; 95% CI:2.21-3.71) compared to men, higher among African Americans (OR=2.37, 95% CI:1.41-3.99) compared to Caucasians, and higher among those who were overweight (OR=1.48; 95% CI:1.11-1.98) or obese (OR= 1.73; 95% CI:1.26-2.38) compared to those of normal weight. The variant m.16362T >C (rs62581341) in the mitochondrial control region was positively associated with grade 2/3 meningiomas (OR=2.33; 95% CI: 1.14-4.79), but not with grade 1 tumors (OR=0.99; 95% CI:0.64-1.53). Haplogroup L, a marker for African ancestry, was identified among 3.6% of controls and 8.6% of cases and was associated with meningioma risk overall (OR=2.56; 95% CI:1.52-4.30). When stratifying by self-reported race, the association between haplogroup L and meningioma was only apparent among the small number of self-reported Caucasians with this haplogroup (OR=6.68; 95% CI=1.66-26.91) when compared to non-L haplogroups, combined. No other common mtDNA variant (minor allele >5%), haplogroup, or gene was associated with meningioma risk. These findings merit further study.

Dataset Information

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

Publications

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

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