对氧磷酶 1（PON1）C/T-108 与纵向平均动脉血压的关联。

Paraoxonase 1 (PON1) C/T-108 association with longitudinal mean arterial blood pressure.

机构信息

Department of Family and Preventive Medicine, University of California San Diego, La Jolla, California, USA.

出版信息

Am J Hypertens. 2012 Nov;25(11):1188-94. doi: 10.1038/ajh.2012.106. Epub 2012 Aug 2.

DOI:10.1038/ajh.2012.106

PMID:22854640

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3515680/

Abstract

BACKGROUND

Blood pressure is a complex quantitative trait with a strong genetic component. In this study, we leveraged the Veterans Affairs electronic medical record system to explore the relationship between Paraoxonase 1 (PON1)-108 C/T (rs705379) and mean arterial blood pressure (MAP).

METHODS

Outpatient blood pressure data over an approximate 8-year period was collected from the Veterans Affairs Hypertensive Cohort (N = 1,302). Association between genotype and longitudinal MAP was further explored using a random effects model controlling for age, ancestry, renal function, and other determinants of blood pressure. To control for population stratification, principal component groupings based on ancestry informative markers in this dataset were included as covariates (in addition to self-identified ancestry). Data from the African American Study of Kidney Disease and Hypertension (AASK, N = 857) was used to confirm significant findings in an independent cohort.

RESULTS

There was a significant interaction between PON1-108 C/T genotype and follow-up age group. At a younger age (<50 years), there was an estimated 2.53 mm Hg (95% confidence interval: 1.06, 4.00) increase in MAP with each additional C-allele. At the older age groups, there were no significant associations between PON1-108 C/T genotype and MAP. Using data from the AASK trial, the C-allele at PON1-108 C/T was significantly associated with a higher MAP (P = 0.005) but only among younger participants (<54 years).

CONCLUSIONS

The PON1-108 polymorphism may be associated with MAP in an age-dependent manner.

摘要

背景

血压是一种具有强遗传成分的复杂定量特征。在这项研究中，我们利用退伍军人事务部电子病历系统来探讨对氧磷酶 1（PON1）-108 C/T（rs705379）与平均动脉压（MAP）之间的关系。

方法

从退伍军人高血压队列（N=1302）中收集了大约 8 年的门诊血压数据。使用随机效应模型，通过控制年龄、祖源、肾功能和血压的其他决定因素，进一步探讨了基因型与纵向 MAP 之间的关系。为了控制群体分层，基于该数据集中的祖源信息标记物的主成分分组被作为协变量（除了自我认定的祖源）包含在内。使用来自非洲裔美国人肾脏病和高血压研究（AASK，N=857）的数据来确认独立队列中的显著发现。

结果

PON1-108 C/T 基因型与随访年龄组之间存在显著的交互作用。在较年轻的年龄组（<50 岁），每增加一个 C 等位基因，MAP 估计增加 2.53mmHg（95%置信区间：1.06，4.00）。在年龄较大的年龄组中，PON1-108 C/T 基因型与 MAP 之间没有显著的关联。使用 AASK 试验的数据，PON1-108 C/T 中的 C 等位基因与 MAP 显著相关（P=0.005），但仅在年龄较小的参与者（<54 岁）中。