Department of Twin Research, King's College London, London, UK.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Am J Hypertens. 2020 May 21;33(6):473-481. doi: 10.1093/ajh/hpaa022.
Epidemiologic and genomic studies have progressively improved our understanding of the causation of hypertension and the complex relationship with diet and environment. The majority of Mendelian forms of syndromic hypotension and hypertension (HTN) have all been linked to mutations in genes whose encoded proteins regulate salt-water balance in the kidney, supporting the primacy of the kidneys in blood pressure regulation. There are more than 1,477 single nucleotide polymorphisms associated with blood pressure and hypertension and the challenge is establishing a causal role for these variants. Hypertension is a complex multifactorial phenotype and it is likely to be influenced by multiple factors including interactions between diet and lifestyle factors, microbiome, and epigenetics. Given the finite genetic variability that is possible in humans, it is likely that incremental gains from single marker analyses have now plateaued and a greater leap in our understanding of the genetic basis of disease will come from integration of other omics and the interacting environmental factors. In this review, we focus on emerging results from the microbiome and metabolomics and discuss how leveraging these findings may facilitate a deeper understanding of the interrelationships between genomics, diet, and microbial ecology in humans in the causation of essential hypertension.
流行病学和基因组学研究逐渐提高了我们对高血压病因以及其与饮食和环境之间复杂关系的认识。大多数综合征性低血压和高血压（HTN）的孟德尔形式都与调节肾脏盐水平衡的基因的突变有关，这支持了肾脏在血压调节中的首要地位。有超过 1477 个单核苷酸多态性与血压和高血压相关，挑战在于确定这些变体的因果作用。高血压是一种复杂的多因素表型，它可能受到多种因素的影响，包括饮食和生活方式因素、微生物组和表观遗传学之间的相互作用。鉴于人类可能存在的有限遗传可变性，单标记分析的增量收益可能已经达到顶峰，而对疾病遗传基础的理解的更大飞跃将来自于整合其他组学和相互作用的环境因素。在这篇综述中，我们重点介绍了微生物组和代谢组学的新成果，并讨论了如何利用这些发现来促进对人类基因组学、饮食和微生物生态学之间相互关系的深入理解，从而更好地了解原发性高血压的病因。
