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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #359263

Research Project: Sarcopenia, Nutrition, and Physical Activity

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Mitochondrial DNA sequence variants associated with blood pressure among 2 cohorts of older adults

Author
item Buford, Thomas - University Of Alabama
item Manini, Todd - University Of Florida
item Kairalla, John - University Of Florida
item Mcdermott, Mary - Northwestern University
item Vaz Fragoso, Carlos - Yale University
item Chen, Haiying - Wake Forest University
item Fielding, Roger - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item King, Abby - Stanford University
item Newman, Anne - University Of Pittsburgh
item Tranah, Gregory - California Pacific Medical Center

Submitted to: Journal of the American Heart Association
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/24/2018
Publication Date: 9/11/2018
Citation: Buford, T.W., Manini, T.M., Kairalla, J.A., McDermott, M.M., Vaz Fragoso, C.A., Chen, H., Fielding, R.A., King, A.C., Newman, A.B., Tranah, G.J. 2018. Mitochondrial DNA sequence variants associated with blood pressure among 2 cohorts of older adults. Journal of the American Heart Association. 7(18):e010009. https://doi.org/10.1161/JAHA.118.010009.
DOI: https://doi.org/10.1161/JAHA.118.010009

Interpretive Summary: Age-related elevations in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age-related increases in blood pressure yet few genetic variations have been identified. In this study, we specifically examined variations in the genes that are located in a specific part of the cell responsible for energy metabolism called the mitochondria by sequencing or measuring the mitochondrial genome. We measured mitochondrial DNA (mtDNA) data from 1,755 participants from the Lifestyle Interventions and Independence for Elders (LIFE) studies and 788 participants from the Health, Aging and Body Composition (Health ABC) Study. Participants were at least 69 years old, of diverse racial backgrounds, and assessed for systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressures. In this study, we found that mtDNA genetic variants are associated with variation in SBP and MAP among older adults. These results may help to identify how mitochondrial function relates to differences in blood pressure in older adults.

Technical Abstract: Background: Age-related changes in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age-related increases in blood pressure yet few genetic loci have been identified. We examined the role of mitochondrial genomic variation on blood pressure by sequencing the mitochondrial genome. Methods and Results: Mitochondrial DNA (mtDNA) data from 1,755 participants from the Lifestyle Interventions and Independence for Elders (LIFE) studies and 788 participants from the Health, Aging and Body Composition (Health ABC) Study were evaluated using replication analysis followed by meta-analysis. Participants were >/=69 years old, of diverse racial backgrounds, and assessed for systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressures. After meta-analysis across the LIFE and Health ABC studies, statistically significant associations of mtDNA variants with higher SBP (m.3197T>C, 16S rRNA; P=0.0005) and MAP (m.15924A>G, tRNA-thr; P=0.004) were identified in white participants. Among black participants, statistically significant associations with higher SBP (m.93A>G, HVII; m.16183A>C, HVI; both P=0.0001)) and MAP (m.16172T>C, HVI; m.16183A>C, HVI; m.16189T>C, HVI; m.12705C>T; all P's<0.0004) were observed. Significant pooled effects on SBP were observed across all tRNA regions (P=0.0056) in white participants. The individual and aggregate variant results are statistically significant after multiple comparisons adjustment for the number of mtDNA variants and mitochondrial regions examined. Conclusions: These results suggest that mtDNA-encoded variants are associated with variation in SBP and MAP among older adults. These results may help to identify mitochondrial activities to explain differences in blood pressure in older adults and generate new hypotheses surrounding mtDNA variation and the regulation of blood pressure.