Genomic determinants of hypertension with a focus on metabolomics and the gut microbiome.

TY - JOUR

T1 - Genomic determinants of hypertension with a focus on metabolomics and the gut microbiome.

AU - Louca, Panayiotis

AU - Menni, Cristina

AU - Padmanabhan, Sandosh

PY - 2020/5/21

Y1 - 2020/5/21

N2 - 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.

AB - 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.

KW - blood pressure

KW - diet

KW - genomics

KW - hypertension

KW - metabolomics

KW - metagenomics

KW - microbiome

KW - salt

UR - http://www.scopus.com/inward/record.url?scp=85085265235&partnerID=8YFLogxK

U2 - 10.1093/ajh/hpaa022

DO - 10.1093/ajh/hpaa022

M3 - Review article

SN - 0895-7061

VL - 33

SP - 473

EP - 481

JO - American Journal of Hypertension

JF - American Journal of Hypertension

IS - 6

ER -