Single nucleotide polymorphisms of the renin angiotensin system linked to
                        high prevalence of essential hypertension in the Taita tribe of Kasigau,
                        Kenya

Several single nucleotide polymorphisms (SNPs) of renin-angiotensin system (RAS) genes are associated with hypertension (HT) but most of them are focusing on single locus effects. Here, we introduce an unbalanced function based on multifactor dimensionality reduction (MDR) for multiloci genotypes to detect high order gene-gene (SNP-SNP) interaction in unbalanced cases and controls of HT data. Eight SNPs of three RAS genes (angiotensinogen,AGT; angiotensin-converting enzyme,ACE; angiotensin II type 1 receptor,AT1R) in HT and non-HT subjects were included that showed no significant genotype differences. In 2- to 6-locus models of the SNP-SNP interaction, the SNPs ofAGTandACEgenes were associated with hypertension (bootstrapping odds ratio [Boot-OR] = 1.972~3.785; 95%, confidence interval (CI) 1.26~6.21;P<0.005). In 7- and 8-locus model, SNP A1166C ofAT1Rgene is joined to improve the maximum Boot-OR values of 4.050 to 4.483; CI = 2.49 to 7.29;P<1.63E−08. In conclusion, the epistasis networks are identified by eight SNP-SNP interaction models.AGT,ACE, andAT1Rgenes have overall effects with susceptibility to hypertension, where the SNPs ofACEhave a mainly hypertension-associated effect and show an interacting effect to SNPs ofAGTandAT1Rgenes.

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Cardiovascular Disease, Single Nucleotide Polymorphisms; and the Renin Angiotensin System: Is There a MicroRNA Connection?

International Journal of Hypertension ◽

10.4061/2010/281692 ◽

2010 ◽

Vol 2010 ◽

pp. 1-13 ◽

Cited By ~ 18

Author(s):

Terry S. Elton ◽

Sarah E. Sansom ◽

Mickey M. Martin

Keyword(s):

Cardiovascular Disease ◽

Single Nucleotide Polymorphisms ◽

Mirna Gene ◽

Renin Angiotensin System ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Angiotensin System ◽

Renin Angiotensin ◽

Ras Genes ◽

Inhibit Gene Expression

Essential hypertension is a complex disorder, caused by the interplay between many genetic variants, gene-gene interactions, and environmental factors. Given that the renin-angiotensin system (RAS) plays an important role in blood pressure (BP) control, cardiovascular regulation, and cardiovascular remodeling, special attention has been devoted to the investigation of single-nucleotide polymorphisms (SNP) harbored in RAS genes that may be associated with hypertension and cardiovascular disease. MicroRNAs (miRNAs) are a family of small,∼21-nucleotide long, and nonprotein-coding RNAs that recognize target mRNAs through partial complementary elements in the3′-untranslated region (3′-UTR) of mRNAs and inhibit gene expression by targeting mRNAs for translational repression or destabilization. Since miRNA SNPs (miRSNPs) can create, destroy, or modify miRNA binding sites, this review focuses on the hypothesis that transcribed target SNPs harbored in RAS mRNAs, that alter miRNA gene regulation and consequently protein expression, may contribute to cardiovascular disease susceptibility.

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Renin-Angiotensin System Single Nucleotide Polymorphisms Are Associated with Bladder Cancer Risk

Current Oncology ◽

10.3390/curroncol28060396 ◽

2021 ◽

Vol 28 (6) ◽

pp. 4702-4708

Author(s):

Maria Samara ◽

Maria Papathanassiou ◽

Ioanna Farmakioti ◽

Maria Anagnostou ◽

Maria Satra ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Risk ◽

Single Nucleotide Polymorphisms ◽

Renin Angiotensin System ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Ras Gene ◽

Single Nucleotide ◽

Angiotensin System ◽

Renin Angiotensin

The renin-angiotensin system (RAS), besides being a major regulator of blood pressure, is also involved in tumor angiogenesis. Emerging evidence suggests a correlation between the use of pharmacologic RAS inhibitors and a delay in urothelial bladder cancer (BC) progression. However, it is unknown whether RAS gene variants may predispose to the development of BC. This study examined the association of RAS single nucleotide polymorphisms (SNPs) including AT1R rs5186, AT2R rs11091046, REN rs12750834, ANG rs4762, and ANG rs699 with the risk of developing non-invasive BC. Peripheral blood samples from 73 patients with T1 urothelial BC (66 men, seven women) and an equal number of healthy subjects (control group) were collected. The TT genotype of the REN rs12750834 SNP (OR: 2.8 [1.3–6.05], p = 0.008) and to a lesser extent the presence of the T allele (OR: 2.3 [1.2–4.48], p = 0.01) conferred a higher risk of BC. The highest risk for BC within SNP carriers of the RAS system was associated with the presence of the CC genotype (OR: 17.6 [7.5–41.35], p < 0.001) and C allele (OR: 17.7 [8.8–35.9], p < 0.001) of the ANG rs699 SNP. The presence of the AT2R rs11091046 SNP, particularly the AA genotype, was associated with a protective effect against developing BC (OR: 0.268 [0.126–057], p < 0.001). In conclusion, these results support the clinical utility of RAS gene SNPs AT2R rs11091046, REN rs12750834, and ANG rs699 in the genetic cancer risk assessment of patients and families with BC.

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