Author
BUFORD, THOMAS - University Of Alabama | |
MANINI, TODD - University Of Florida | |
KAIRALLA, JOHN - University Of Florida | |
MCDERMOTT, MARY - Northwestern University | |
VAZ FRAGOSO, CARLOS - Yale University | |
CHEN, HAIYING - Wake Forest University | |
FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
KING, ABBY - Stanford University | |
NEWMAN, ANNE - University Of Pittsburgh | |
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. |