Metabolomics and incident hypertension among blacks: the atherosclerosis risk in communities study.
Metabolomics and incident hypertension among blacks: the atherosclerosis risk in communities study.
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DOI：
10.1161/hypertensionaha.113.01166
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发表时间：
2013-08
期刊：
影响因子：
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通讯作者：
Boerwinkle E
中科院分区：
文献类型：
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作者：
Zheng Y;Yu B;Alexander D;Mosley TH;Heiss G;Nettleton JA;Boerwinkle E
高血压的发生受基因、环境效应及其相互作用的影响，而人体代谢组学是基因-环境相互作用的可测量的表现。我们在非裔美国人样本中探讨了发生高血压的代谢组学前因，非裔美国人是高血压及其合并症的高患病率人群。我们检查了来自社区动脉粥样硬化风险（ARIC）研究的896名（565名女性，年龄45-64岁）非裔美国人血压正常者，其代谢组在基线检查时收集的血清中进行测量，并通过高通量方法进行分析。本文中的分析集中在4-6周内稳定测量的204种代谢物。考虑区间删失数据的威布尔参数模型被用来评估高血压事件的风险比。我们使用修正的Bonferroni校正来解释代谢物之间的相关性，以定义统计学显著性的阈值（p<3.9×10−4）。在10年的随访中，38%的基线血压正常者发展为高血压（N=344）。校正传统风险因素和估计的肾小球滤过率后，基线4-羟基马尿酸（肠道微生物发酵产物）的每+1标准差差异与高血压风险增加17%相关（p=2.5×10−4），在校正基线收缩压和舒张压后仍显着（p=3.8×10−4）。主成分分析后，性类固醇模式与高血压事件风险显著相关（最高与最低五分位风险比，1.72; 95%CI，1.05 - 2.82;趋势p =0.03），分层分析表明这种关联在两种性别中是一致的。代谢组学分析确定了高血压病因学的新途径。
Development of hypertension is influenced by genes, environmental effects and their interactions, and the human metabolome is a measurable manifestation of gene-environment interaction. We explored the metabolomic antecedents of developing incident hypertension in a sample of African Americans, a population with a high prevalence of hypertension and its comorbidities. We examined 896 (565 females, aged 45–64 years) African American normotensives from the Atherosclerosis Risk in Communities (ARIC) Study, whose metabolome was measured in serum collected at the baseline examination and analyzed by high throughput methods. The analyses presented here focus on 204 stably measured metabolites over a period of 4–6 weeks. Weibull parametric models considering interval censored data were used to assess the hazard ratio for incident hypertension. We used a modified Bonferroni correction accounting for the correlations among metabolites to define a threshold for statistical significance (p<3.9×10−4). During 10-years of follow-up, 38% of baseline normotensives developed hypertension (N=344). With adjustment for traditional risk factors and estimated glomerular filtration rate, each +1-standard deviation difference in baseline 4-hydroxyhippurate, a product of gut microbial fermentation, was associated with 17% higher risk of hypertension (p=2.5×10−4), which remained significant after adjusting for both baseline systolic and diastolic blood pressure (p=3.8×10−4). After principal component analyses, a sex steroids pattern was significantly associated with risk of incident hypertension (highest versus lowest quintile hazard ratio, 1.72; 95% CI, 1.05 to 2.82; p for trend=0.03), and stratified analyses suggested that this association was consistent in both genders. Metabolomic analyses identify novel pathways in the etiology of hypertension.