|(A;C)||2.1||~1.4x increased risk of hypertension|
|(C;C)||4||7.3x increased risk of hypertension|
rs5186, a SNP known as +1166A/C or A1166C, is located in the 3' untranslated region of the angiotensin II receptor type 1 gene AGTR1, which is also known as AT2R1 or AT1R. It is among the most studied of over 50 SNPs in AGTR1.
The rs5186(C) allele is associated with increased risk for essential hypertension in Caucasian populations with an odds ratio of 7.3 (homozygote (C;C) compared to (A;C) and (A;A), CI: 1.9-31.9,p=0.0015).[PMID 8021009, PMID 9084931] There are likely to be ethnic differences in risk; while the rs5186(C) allele was associated with hypertension in a Chinese population [PMID 11793845], it was not been observed as a risk in a Japanese population.[PMID 12627871] Age and gender may also influence risk, as discussed in a review of AGTR1 SNPs and their role in hypertension and related disorders.[PMID 15640279]
However, rs5186 does not appear to modify risk for developing coronary heart disease (CHD). A literature-based meta-analysis of studies published before June 2008 and totaling over 20,000 CHD cases concluded that there were no significant associations among the larger sample-size and high-quality studies.[PMID 20732682]
- C @ chr3:148459988: 21.5% (985/4584) in EVS
- C @ chr3:149942677: 19.5% (25/128) in GET-Evidence
- Frequency shown in summary reports: 21.5% (985/4584)
[PMID 19619703] Association of genetic variants with the metabolic syndrome in 20,806 white women: The women's health genome study
[PMID 19330904] Genetic polymorphisms of the angiotensin II type 1 receptor gene and diastolic heart failure.
[PMID 19954723] The A1166C polymorphism of angiotensin II Type 1 receptor as a predictor of renal function decline over 4 years follow-up in an apparently healthy Chinese population
[PMID 20864943] Early Inflammatory and Metabolic Changes in Association With AGTR1 Polymorphisms in Prehypertensive Subjects
[PMID 20570668] Genetic associations with mountain sickness in Han and Tibetan residents at the Qinghai-Tibetan Plateau
[PMID 21671168] Association of polymorphisms in angiotensin II receptor genes with aldosterone-producing adenoma
[PMID 21722816] Contribution of Deletion in Angiotensin-converting Enzyme But Not A1166C Angiotensin II Type-1 Receptor Gene Polymorphisms to Clinical Outcomes in Atherothrombotic Disease
[PMID 22508051] Renin-Angiotensin-aldosterone system gene polymorphisms and coronary artery disease: detection of gene-gene and gene-environment interactions
[PMID 22569109] The role of renin-angiotensin-aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy
[PMID 22645060] Association study of angiotensin II type 1 receptor: A1166C (rs5186) polymorphism with coronary heart disease using systematic meta-analysis
[PMID 16175505] Identification of four gene variants associated with myocardial infarction.
[PMID 17173513] No association between variants in the ACE and angiotensin II receptor 1 genes and acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at 4380 m.
[PMID 17207964] Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels.
[PMID 17211857] Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits.
[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 18224312] Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
[PMID 18279468] Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure.
[PMID 18413494] Hereditary determinants of human hypertension: strategies in the setting of genetic complexity.
[PMID 18513389] New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.
[PMID 18637188] RAS gene polymorphisms, classical risk factors and the advent of coronary artery disease in the Portuguese population.
[PMID 18641512] Angiotensin II type 1 receptor polymorphisms and susceptibility to hypertension: a HuGE review.
[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 19290790] MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine.
[PMID 19330901] Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.
[PMID 19336370] Determination of genetic predisposition to patent ductus arteriosus in preterm infants.
[PMID 19371411] dbSMR: a novel resource of genome-wide SNPs affecting microRNA mediated regulation.
[PMID 19379518] Development of a fingerprinting panel using medically relevant polymorphisms.
[PMID 19559392] A candidate gene association study of 77 polymorphisms in migraine.
[PMID 19587357] A systematic meta-analysis of genetic association studies for diabetic retinopathy.
[PMID 19716087] Genetic variation in angiotensin-converting enzyme-related pathways associated with sudden cardiac arrest risk.
[PMID 20308035] Common genetic variation, residential proximity to traffic exposure, and left ventricular mass: the multi-ethnic study of atherosclerosis.
[PMID 20428464] MicroRNA polymorphisms: a giant leap towards personalized medicine.
[PMID 20486282] Genetic variants in the renin-angiotensin-aldosterone system and salt sensitivity of blood pressure.
[PMID 20565774] Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.
[PMID 21304999] Epistatic interactions in genetic regulation of t-PA and PAI-1 levels in a Ghanaian population.
[PMID 21316998] A polymorphism in the angiotensin II type 1 receptor gene has different effects on the risk of diabetic nephropathy in men and women.
[PMID 21346624] Interactive effect of angiotensin II type 1 receptor (AGT1R) polymorphisms and plasma irbesartan concentration on antihypertensive therapeutic responses to irbesartan.
[PMID 21771600] A polymorphic miR-155 binding site in AGTR1 is associated with cardiac hypertrophy in Friedreich ataxia.
[PMID 21799445] Genetic variants in the renin-angiotensin-aldosterone system and blood pressure responses to potassium intake.
[PMID 22433249] Genetic polymorphisms located in TGFB1, AGTR1, and VEGFA genes are associated to chronic renal allograft dysfunction.
[PMID 22664914] MicroRNA-mediated regulation of gene expression is affected by disease-associated SNPs within the 3'-UTR via altered RNA structure.
[PMID 17588946] The human angiotensin II type 1 receptor +1166 A/C polymorphism attenuates microrna-155 binding.
[PMID 23081748] ACACβ gene (rs2268388) and AGTR1 gene (rs5186) polymorphism and the risk of nephropathy in Asian Indian patients with type 2 diabetes
|qualified_impact||Low clinical importance, Likely pathogenic|
|summary||This common noncoding genetic variant has an allele frequency of ~30% and is associated with an increased risk of hypertension. If ~25% of non-carriers have hypertension, Bonnardeaux et al's data predict ~4% increased risk of hypertension per copy of this variant. This SNP is in the 3' noncoding region of the AGTR1 transcript (angiotensin II type 1 receptor), also known as AT2R1 or AT1R, which is a target of hypertension drugs.|
[PMID 23132613] Genetic association studies in pre-eclampsia: systematic meta-analyses and field synopsis
[PMID 23339167] Single nucleotide polymorphisms in G protein signaling pathway genes in preeclampsia.
[PMID 24801553] Analysis of multiple genetic polymorphisms in aggressive-growing and slow-growing abdominal aortic aneurysms
[PMID 24860821] Gender Specific Association of RAS Gene Polymorphism with Essential Hypertension: A Case-Control Study
[PMID 24978482] Polymorphisms in genes of the renin-angiotensin-aldosterone system and renal cell cancer risk: Interplay with hypertension and intakes of sodium, potassium and fluid
[PMID 24981111] Impact of the AGTR1 A1166C polymorphism on subcortical hyperintensities and cognition in healthy older adults
[PMID 25020710] P324Circadian genes in the regulation of lipids in coronary artery disease
|CLNDBN||Hypertension, essential, susceptibility to|
|CLNSRC||ClinVar NCBI curation OMIM Allelic Variant|