Maternal influence on blood pressure suggests involvement of mitochondrial DNA in the pathogenesis of hypertension: the Framingham Heart Study.
OBJECTIVE
To investigate the contribution of the mitochondrial genome to hypertension and quantitative blood pressure (BP) phenotypes in the Framingham Heart Study cohort, a randomly ascertained, community-based sample.


METHODS
Longitudinal BP values of 6421 participants (mean age, 53 years; 46% men) from 1593 extended families were used for analyses. In analyses of BP as a continuous trait, a variance components model with a variance component for maternal effects was used to estimate the mitochondrial heritability of the long-term average BP adjusted for age, sex, body mass index, and hypertension treatment. For analyses of BP as a categorical trait, a nonparametric test sensitive to excessive maternal inheritance was used to test for mitochondrial effect on long-term hypertension, defined as systolic BP of at least 140 mmHg or diastolic BP of at least 90 mmHg or use of antihypertensive medication in one-half or more of qualifying examinations. This test was based on 353 pedigrees comprised of 403 individuals informative for mitochondrial DNA contribution.


RESULTS
The estimated fraction of hypertensive pedigrees potentially due to mitochondrial effects was 35.2% (95% confidence interval, 27-43%, P < 10). The mitochondrial heritabilities for multivariable-adjusted long-term average systolic BP and diastolic BP were, respectively, 5% (P < 0.02) and 4% (P = 0.11).


CONCLUSIONS
Our data provide support for a maternal effect on hypertension status and quantitative systolic BP, consistent with mitochondrial influence. Additional studies are warranted to identify mitochondrial DNA variant(s) affecting BP.
Yang
Qiong
Q
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Kim
Sung K
SK
Sun
Fengzhu
F
Cui
Jing
J
Larson
Martin G
MG
Vasan
Ramachandran S
RS
Levy
Daniel
D
Schwartz
Faina
F
D001794:Blood Pressure / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D054629:Genome, Mitochondrial; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts; D008957:Models, Genetic; D009035:Mothers; D010375:Pedigree; D010641:Phenotype; D018709:Statistics, Nonparametric
D004272:DNA, Mitochondrial