The transcriptional regulation of the human angiotensinogen gene after high-fat diet is haplotype-dependent: Novel insights into the gene-regulatory networks and implications for human hypertension

Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the...

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Bibliographic Details
Published in:PloS one 2017-05, Vol.12 (5), p.e0176373-e0176373
Main Authors: Rana, Anita, Jain, Sudhir, Puri, Nitin, Kaw, Meenakshi, Sirianni, Natalie, Eren, Deniz, Mopidevi, Brahma Raju, Kumar, Ashok
Format: Article
Language:English
Subjects:
Adipose tissue
Aldosterone
Angiotensin
Angiotensinogen
Angiotensinogen - genetics
Animal tissues
Binding
Biology and life sciences
Blood
Blood pressure
Care and treatment
Chromatin
Cytokines
Development and progression
Diet
Diet, High-Fat
Gene expression
Gene Expression Regulation
Gene regulation
Gene Regulatory Networks
Genetic aspects
Genetic regulation
Haplotypes
Health aspects
High fat diet
Humans
Hypertension
Hypertension - genetics
Identification and classification
Kinases
Liver
Medicine and Health Sciences
Mice
Obesity
Pharmacology
Physiology
Plasma levels
Proteins
Renin
Rodents
Signal transduction
Single-nucleotide polymorphism
Stat3 protein
Transcription factors
Transcription, Genetic
Transgenic mice
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Summary:Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have made transgenic mice (TG) containing either Hap I or Hap II of the hAGT gene to understand the role of obesity on its transcriptional regulation. Although, a high-fat diet (60% Kcal from fat, 12 weeks) elevates hAGT and mAGT regardless of haplotype, this effect is significantly (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0176373