ArticleAmerican journal of human genetics2004
Natural selection and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequences in chromosomes from around the world.
Article in American journal of human genetics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- AGT, CYP11B2 & ADRB2 gene polymorphism & essential hypertension (HT): A meta-analysis.The Indian journal of medical research · 2024Pooled it
- Article
- Renin-Angiotensin-Aldosterone System: From History to Practice of a Secular Topic.International journal of molecular sciences · 2024Review
- Genetic Factors Contributing to the Pathogenesis of Essential Hypertension in Two African Populations.Journal of personalized medicine · 2024Article
- Identifying signatures of positive selection in human populations from North Africa.Scientific reports · 2023Article
- Identifying Genomic Signatures of Positive Selection to Predict Protective Genomic Loci in the Cohort of Lithuanian Clean-Up Workers of the Chornobyl Nuclear Disaster.Current issues in molecular biology · 2023Article
- Evolution of Human-Specific Alleles Protecting Cognitive Function of Grandmothers.Molecular biology and evolution · 2022Article
- Evolutionary forces in diabetes and hypertension pathogenesis in Africans.Human molecular genetics · 2021Review
- Natural Selection ofFrontiers in genetics · 2021Article
- Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension.International journal of molecular sciences · 2020Review
- COVID's Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Review
- Pharmacogenomics of amlodipine and hydrochlorothiazide therapy and the quest for improved control of hypertension: a mini review.Heart failure reviews · 2019Review
- Natural selection and local adaptation of blood pressure regulation and their perspectives on precision medicine in hypertension.Hereditas · 2019Review
- Genetic variability of five ADRB2 polymorphisms among Mexican Amerindian ethnicities and the Mestizo population.PloS one · 2019Article
- Angiotensin II- and Alzheimer-Type Cardiovascular Aging.Circulation research · 2018Article
- Towards Precision Medicine for Hypertension: A Review of Genomic, Epigenomic, and Microbiomic Effects on Blood Pressure in Experimental Rat Models and Humans.Physiological reviews · 2017Review
- Genetic signature of strong recent positive selection at interleukin-32 gene in goat.Asian-Australasian journal of animal sciences · 2017Article
- Positive selection of IL-33 in adaptive immunity of domestic Chinese goats.Ecology and evolution · 2017Article
- Article
- Quantification of intact plasma AGT consisting of oxidized and reduced conformations using a modified ELISA.American journal of physiology. Renal physiology · 2016Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 11 institutions in 4 countries.
Funding
Abstract
Several lines of evidence suggest that patterns of genetic variability in the human angiotensinogen gene (AGT) contribute to phenotypic variability in human hypertension. The A(-6) promoter variant of AGT is associated with higher plasma angiotensinogen levels and increased risk of essential hypertension. The geographic distribution of the A(-6) variant leads to the intriguing hypothesis that the G(-6) promoter variant has been selectively advantageous outside Africa. To test these hypotheses, we investigated the roles of population history and natural selection in shaping patterns of genetic diversity in AGT, by sequencing the entire AGT gene (14400 bp) in 736 chromosomes from Africa, Asia, and Europe. We found that the A(-6) variant is present at higher frequency in African populations than in non-African populations. Neutrality tests found no evidence of a departure from selective neutrality, when whole AGT sequences were compared. However, tests restricted to sites in the vicinity of the A(-6)G polymorphism found evidence of a selective sweep. Sliding-window analyses showed that evidence of the sweep is restricted to sites in tight linkage disequilibrium (LD) with the A(-6)G polymorphism. Further, haplotypes carrying the G(-6) variant showed elevated levels of LD, suggesting that they have risen recently to high frequency. Departures from neutral expectation in some but not all regions of AGT indicate that patterns of diversity in the gene cannot be accounted for solely by population history, which would affect all regions equally. Taken together, patterns of genetic diversity in AGT suggest that natural selection has generally favored the G(-6) variant over the A(-6) variant in non-African populations. However, important localized effects may also be present.
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