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Intrinsic and extrinsic epigenetic age acceleration are associated with hypertensive target organ damage in older African Americans.
- Source :
-
BMC medical genomics [BMC Med Genomics] 2019 Oct 22; Vol. 12 (1), pp. 141. Date of Electronic Publication: 2019 Oct 22. - Publication Year :
- 2019
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Abstract
- Background: Epigenetic age acceleration, a measure of biological aging based on DNA methylation, is associated with cardiovascular mortality. However, little is known about its relationship with hypertensive target organ damage to the heart, kidneys, brain, and peripheral arteries.<br />Methods: We investigated associations between intrinsic (IEAA) or extrinsic (EEAA) epigenetic age acceleration, blood pressure, and six types of organ damage in a primarily hypertensive cohort of 1390 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. DNA methylation from peripheral blood leukocytes was collected at baseline (1996-2000), and measures of target organ damage were assessed in a follow-up visit (2000-2004). Linear regression with generalized estimating equations was used to test for associations between epigenetic age acceleration and target organ damage, as well as effect modification of epigenetic age by blood pressure or sex. Sequential Oligogenic Linkage Analysis Routines (SOLAR) was used to test for evidence of shared genetic and/or environmental effects between epigenetic age acceleration and organ damage pairs that were significantly associated.<br />Results: After adjustment for sex, chronological age, and time between methylation and organ damage measures, higher IEAA was associated with higher urine albumin to creatinine ratio (UACR, p = 0.004), relative wall thickness (RWT, p = 0.022), and left ventricular mass index (LVMI, p = 0.007), and with lower ankle-brachial index (ABI, p = 0.014). EEAA was associated with higher LVMI (p = 0.005). Target organ damage associations for all but IEAA with LVMI remained significant after further adjustment for blood pressure and antihypertensive use (p < 0.05). Further adjustment for diabetes attenuated the IEAA associations with UACR and RWT, and adjustment for smoking attenuated the IEAA association with ABI. No effect modification by age or sex was observed.<br />Conclusions: Measures of epigenetic age acceleration may help to better characterize the functional mechanisms underlying organ damage from cellular aging and/or hypertension. These measures may act as subclinical biomarkers for damage to the kidney, heart, and peripheral vasculature; however more research is needed to determine whether these relationships remain independent of lifestyle factors and comorbidities.
- Subjects :
- Age Factors
Aged
Ankle Brachial Index
Antihypertensive Agents therapeutic use
Blood Pressure
Creatinine urine
DNA Methylation
Female
Glomerular Filtration Rate
Heart Ventricles chemistry
Humans
Hypertension drug therapy
Leukocytes, Mononuclear metabolism
Linear Models
Male
Middle Aged
Risk Factors
Serum Albumin, Human urine
Black or African American genetics
Epigenesis, Genetic
Hypertension pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1755-8794
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC medical genomics
- Publication Type :
- Academic Journal
- Accession number :
- 31640709
- Full Text :
- https://doi.org/10.1186/s12920-019-0585-5