内在和外在的表观遗传年龄加速与老年非裔美国人的高血压靶器官损伤有关。
Intrinsic and extrinsic epigenetic age acceleration are associated with hypertensive target organ damage in older African Americans.
机构信息
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
出版信息
BMC Med Genomics. 2019 Oct 22;12(1):141. doi: 10.1186/s12920-019-0585-5.
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.
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.
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.
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.
背景
基于 DNA 甲基化的表观遗传年龄加速是衡量生物衰老的一个指标，与心血管死亡率相关。然而，人们对其与高血压对心脏、肾脏、大脑和外周动脉的靶器官损害的关系知之甚少。
方法
我们在主要为高血压的非洲裔美国人的遗传流行病学网络动脉粥样硬化（GENOA）研究的一个队列中，研究了内在（IEAA）或外在（EEAA）表观遗传年龄加速与血压和六种类型的器官损害之间的关联。在基线（1996-2000 年）采集外周血白细胞的 DNA 甲基化样本，并在随访时（2000-2004 年）评估靶器官损害的指标。使用广义估计方程的线性回归检验表观遗传年龄加速与靶器官损害之间的关联，以及血压或性别对表观遗传年龄的影响修饰作用。使用连锁分析规则（SOLAR）测试表观遗传年龄加速与显著相关的器官损害对之间是否存在共享遗传和/或环境效应的证据。
结果
在校正性别、实际年龄和 DNA 甲基化与器官损害测量之间的时间后，较高的 IEAA 与较高的尿白蛋白/肌酐比值（UACR，p=0.004）、相对壁厚度（RWT，p=0.022）和左心室质量指数（LVMI，p=0.007）相关，与较低的踝臂指数（ABI，p=0.014）相关。EEAA 与 LVMI 较高相关（p=0.005）。除了与 LVMI 相关的 IEAA 之外，所有器官损害的关联在进一步校正血压和降压药物使用后仍然显著（p<0.05）。IEAA 与 UACR 和 RWT 的关联在进一步校正糖尿病后减弱，IEAA 与 ABI 的关联在调整吸烟后减弱。年龄或性别无修饰作用。
结论
表观遗传年龄加速的指标可能有助于更好地描述细胞衰老和/或高血压引起的器官损害的功能机制。这些指标可以作为肾脏、心脏和外周血管损害的亚临床生物标志物；然而，需要更多的研究来确定这些关系是否仍然独立于生活方式因素和合并症。
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