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rs699

Chromosome : 1 , Position: 230710048
Most conditions are affected by anywhere from hundreds to millions of genetic variants (SNPs). A single SNP usually has a minor contribution to a person’s overall genetic risk for a certain condition. That is why you shouldn't consider or act on a SNP in isolation. Instead, we use SNPs to determine polygenic risk scores (PRSs), which are the basis of most health reports.
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Reference AlleleA
Alternative Alleles:  G

Traits

Trait Variant Impact PMID Author (year)
Mean arterial pressure G
Nat Genet Liu C (2016)
Systolic blood pressure G
Nat Genet Giri A (2018)
Coronary artery disease G
Circ Res van der Harst P (2017)

Summary

rs699 is a SNP in the angiotensin AGT gene that encodes a functional change. In most published literature, the name for this SNP is M235T, or perhaps Met235Thr, however its amino acid 268 (not 235) that varies based on the numbering in todays databases. rs699 is also occasionally known as C4072T.

In any case, the rs699(C) allele encodes the threonine variant, which is associated with higher plasma angiotensin levels, and ultimately higher blood pressure leading to increased risk for hypertension associated disorders.

This association was first reported in 1992 [pre-eclampsia (pregnancy-induced hypertension)[PMID 8513325, PMID 8348146] but did not present a risk in one African population [PMID 16059745].

[PMID 19108684] A haplotype of rs4311, rs4343, rs699 increases risk of diabetic nephropathy 4x.




[PMID 18653189] Interaction of gender, hypertension, and the angiotensinogen gene haplotypes on the risk of coronary artery disease in a large angiographic cohort


[PMID 19932491] Angiotensinogen polymorphisms and acquired atrial fibrillation in Chinese


[PMID 20029521] The C allele of the AGT Met235Thr polymorphism is associated with power sports performance


[PMID 20185782] Renin Angiotensin System Gene Polymorphisms and Cerebral Blood Flow Regulation. The MOBILIZE Boston Study


[PMID 20592051] Interactions among related genes of renin-angiotensin system associated with type 2 diabetes



[PMID 20570668] Genetic associations with mountain sickness in Han and Tibetan residents at the Qinghai-Tibetan Plateau


[PMID 21261619] Genetic variation in renin predicts the effects of thiazide diuretics

[PMID 21306748] The association of the angiotensinogen gene with insulin sensitivity in humans: a tagging single nucleotide polymorphism and haplotype approach


[PMID 21988197] Angiotensinogen gene haplotype is associated with the prevalence of Japanese non-alcoholic steatohepatitis


[PMID 22508051] Renin-Angiotensin-aldosterone system gene polymorphisms and coronary artery disease: detection of gene-gene and gene-environment interactions


[PMID 22531885] Revising the M235T Polymorphism Position for the AGT Gene and Reporting a Modifying Variant in the Brazilian Population with Potential Cardiac and Neural Impact


[PMID 22569109] The role of renin-angiotensin-aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy




[PMID 18069999] Renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms are not associated with the risk of incident type 2 diabetes mellitus: a prospective cohort study.


[PMID 18248681] Prevalence of common disease-associated variants in Asian Indians.


[PMID 18279468] Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure.


[PMID 18513389] New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.


[PMID 18603647] Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.


[PMID 18637188] RAS gene polymorphisms, classical risk factors and the advent of coronary artery disease in the Portuguese population.


[PMID 18698212] Association of renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms with blood pressure progression and incident hypertension: prospective cohort study.


[PMID 18953568] Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population.


[PMID 19131662] A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.


[PMID 19263529] Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.


[PMID 19330901] Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women’s Genome Health Study.


[PMID 19559392] A candidate gene association study of 77 polymorphisms in migraine.


[PMID 20061926] Randomized controlled trial: lisinopril reduces proteinuria, ammonia, and renal polypeptide tubular catabolism in patients with chronic allograft nephropathy.


[PMID 20486282] Genetic variants in the renin-angiotensin-aldosterone system and salt sensitivity of blood pressure.


[PMID 21304999] Epistatic interactions in genetic regulation of t-PA and PAI-1 levels in a Ghanaian population.


[PMID 21438754] Gene variation in resistant hypertension: multilocus analysis of the angiotensin 1-converting enzyme, angiotensinogen, and endothelial nitric oxide synthase genes.




[PMID 23132613] Genetic association studies in pre-eclampsia: systematic meta-analyses and field synopsis


[PMID 23681449] Genes for Elite Power and Sprint Performance: ACTN3 Leads the Way


[PMID 23681285] Association of aldosterone synthase (CYP11B2) gene -344T/C polymorphism with the risk of primary chronic glomerulonephritis in the Polish population


[PMID 23716723] The Relationship Between Angiotensinogen Gene Polymorphisms and Essential Hypertension in a Northern Han Chinese Population


[PMID 24622918] Renin-Angiotensin System Genetic Polymorphisms and Brain White Matter Lesions in Older Australians


[PMID 22858200] Angiotensinogen gene polymorphisms and food-intake behavior in young, normal female subjects in Japan.


[PMID 23021345] Gene-diet interactions on plasma lipid levels in the Inuit population.


[PMID 23251296] Assessment of two missense polymorphisms (rs4762 and rs699) of the angiotensinogen gene and stroke.


[PMID 23333443] Analysis of polymorphisms and haplotypes in genes associated with vascular tone, hypertension and oxidative stress in Mexican-Mestizo women with severe preeclampsia.


[PMID 23354977] Human loci involved in drug biotransformation: worldwide genetic variation, population structure, and pharmacogenetic implications.


[PMID 24860821] Gender Specific Association of RAS Gene Polymorphism with Essential Hypertension: A Case-Control Study


[PMID 25020710] P324Circadian genes in the regulation of lipids in coronary artery disease


[PMID 25683681] Positive Association of D Allele of ACE Gene With High Altitude Pulmonary Edema in Indian Population


[PMID 24722536] Relationship of renin-angiotensin-aldosterone system polymorphisms and phenotypes to mortality in Chinese coronary atherosclerosis patients

More Information

The G (major) allele is associated with:

  • Increased risk of hypertension [R].
  • Increased risk of pre-eclampsia during pregnancy [R].
  • Greater improvements in power-based fitness [R]
  • More prevalent in power-based athlete populations [R, R]

 

Population Alleles Frequency

ethhicity frequency
African/African-American 0.8329
Latino/Admixed American 0.6769
Ashkenazi Jewish 0.4241
East Asian 0.8397
European 0.4398
Other (population not assigned) 0.4705

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