Genetic Variation in the Renin-Angiotensin System and Autonomic Nervous System Function in Young Healthy Japanese Subjects

Nishikino, Mariko; Matsunaga, Tetsuro; Yasuda, Koichiro; Adachi, Tomohiko; Moritani, Toshio; Tsujimoto, Gozoh; Tsuda, Kinsuke; Aoki, Norihiko

doi:10.1210/jc.2006-0700

Cited by 22 publications

(18 citation statements)

References 39 publications

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“…7 This suggests that the effect of AII may be enhanced in carriers of the C allele of the AT1R A1166C polymorphism. 4,[25][26][27] It is noted that AII infusion decreases plasma adiponectin levels through its type 1 receptor in rats, 10 and treatment with an AII type 1 receptor antagonist increases plasma adiponectin levels in hypertensive patients. 12 These results suggest that a difference in activation of the local RAS may be directly involved in the variation between genotypes with regard to plasma adiponectin concentrations.…”

Section: Discussionmentioning

confidence: 99%

C allele of angiotensin II type 1 receptor gene A1166C polymorphism affects plasma adiponectin concentrations in healthy young Japanese women

et al. 2009

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Angiotensin II and its type 1 receptor (AT1R) are both expressed in the adipose tissue and involved in the genesis of atherosclerosis as well as hypertension. However, the influence of the AT1R gene A1166C polymorphism on atherosclerosis risk factors and on the development of early atherosclerosis is not clear. We evaluated 416 healthy young women to investigate the effects of this genotype on atherosclerosis risk factors and on carotid intima-media thickness as a validated marker of early atherosclerosis. After adjusting for confounding factors including body mass index, homeostasis model assessment of insulin resistance and plasma high-density lipoprotein (HDL)-cholesterol levels, plasma adiponectin concentrations were significantly lower in carriers of the C allele compared with non-carriers. Moreover, multiple logistic regression analysis showed that the C allele was the strongest and most independent determinant of lower plasma adiponectin concentrations. It is noted that the participants with the lowest quartile of plasma adiponectin concentrations had thicker levels of carotid intima-media thickness, lower plasma HDL-cholesterol and lipoprotein lipase levels, as well as higher trunk fat mass compared with the highest quartile. In addition, a weak but significant positive correlation was observed between percentages of fat in the diet and plasma adiponectin concentrations in non-carriers of the C allele. In conclusion, AT1R A1166C was associated with plasma adiponectin concentrations and influenced the correlations between dietary fat intake and plasma concentrations of adiponectin. These findings may help to identify vulnerable populations that are susceptible to the development of atherosclerosis and require early dietary recommendations for young women.

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Section: Discussionmentioning

confidence: 99%

C allele of angiotensin II type 1 receptor gene A1166C polymorphism affects plasma adiponectin concentrations in healthy young Japanese women

et al. 2009

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“…The few studies conducted thus far, have found no association between rs5186 genotype and blood pressure variation whether studied in population-based cohorts, [107][108][109] hypertensives off antihypertensive medication, 110 -112 or nonhypertensive populations. 94,95,98,113,114 The lack of a functional role of the rs5186 polymorphism makes this SNP somewhat unappealing as a "true" influence of hypertension susceptibility. The available evidence for functionality of AGTR1 polymorphisms is mostly confined to those within the promoter region.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II type 1 receptor polymorphisms and susceptibility to hypertension: A HuGE review

Mottl

Shoham

North

2008

Genetics in Medicine

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The angiotensin II type 1 receptor (AGTR1) plays an integral role in blood pressure control, and is implicated in the pathogenesis of hypertension. Polymorphisms within this gene have been extensively studied in association with hypertension; however, findings are conflicting. To clarify these data, we conducted a systematic review of association studies of AGTR1 polymorphisms and hypertension, and performed a meta-analysis of the rs5186 variant. Results show that the currently available literature is too heterogeneous to draw meaningful conclusions.The definition of hypertension and gender composition of individual studies helps to explain this heterogeneity.Although the structure and splicing pattern of AGTR1 would suggest a likely effect of polymorphisms within the promoter region on gene function, few studies have been conducted thus far. In conclusion, there is insufficient evidence that polymorphisms in the AGTR1 gene are risk factors for hypertension. However, most studies are inadequately powered, and larger well-designed studies of haplotypes are warranted. Genet Med 2008:10 (8): 560 -574.

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“…Indeed, it has been argued that simply modeling genetic polymorphisms as independent and additive effects on the phenotype is not a realistic biological model and that epistasis should be included, 14 although others have questioned the relative importance of epistasis in complex traits. 15 Many studies have tested for epistasis in relation to polymorphisms of RAAS genes and have suggested interactions between AGT and ACE, 9,[16][17][18] between multiple genes, 19 and within haplotypes comprised of certain combinations of variants within individual genes. [20][21][22][23][24] Other studies have been unable to identify evidence that might indicate epistasis.…”

Section: Scurrah Et Al Raas Genes and Blood Pressure In Familiesmentioning

confidence: 99%

“…Many studies have tested for epistasis in relation to polymorphisms of RAAS genes and have suggested interactions between AGT and ACE, 9,[16][17][18] between multiple genes, 19 and within haplotypes comprised of certain combinations of variants within individual genes. [20][21][22][23][24] Other studies have been unable to identify evidence that might indicate epistasis.…”

mentioning

confidence: 99%

Familial Analysis of Epistatic and Sex-Dependent Association of Genes of the Renin–Angiotensin–Aldosterone System and Blood Pressure

Scurrah

Lamantia

Ellis

et al. 2017

Circ Cardiovasc Genet

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T he renin-angiotensin-aldosterone system (RAAS) has a central role in the physiology of blood pressure and is implicated in the pathogenesis of hypertension and cardiovascular disease. The RAAS cascade begins with the rate-limiting cleavage of angiotensinogen (AGT) by renin to produce angiotensin I (Ang I). 1 The subsequent conversion by the angiotensin-converting enzyme (ACE) of Ang I forms angiotensin II (Ang II) that is responsible for a broad range of physiological actions, many of which are mediated through the angiotensin receptor type 1 (AT 1 ), including vasoconstriction and the release of aldosterone from the adrenal glands. Ang II and aldosterone are the classical effectors of the RAAS with complementary actions to raise blood pressure. The enzymes, hormones, and receptors of the RAAS provide targets for effective therapies for hypertension and cardiovascular disease. They also have been popular candidates for genetic studies. See Editorial by Brian J. Morris See Clinical PerspectiveSeveral reviews and meta-analyses summarize the vast number of studies of the RAAS genes in cardiovascular physiology, disease, and treatment. [2][3][4] Genes encoding renin (REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin type 1 receptor (AGTR1), and aldosterone synthase (CYP11B2) feature prominently. Functional polymorphisms in these genes have been associated with significant variation in the levels of RAAS components including angiotensinogen, ACE, and renin.2 They have also been associated with high blood pressure and other cardiovascular diseases including coronary artery disease, preeclampsia and diabetic nephropathy. The results of gene studies of individual RAAS candidates have been heterogeneous in terms of the nature of the Background-Renin-angiotensin-aldosterone system genes have been inconsistently associated with blood pressure, possibly because of unrecognized influences of sex-dependent genetic effects or gene-gene interactions (epistasis). Methods and Results-We tested association of systolic blood pressure with single-nucleotide polymorphisms (SNPs) at renin (REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and aldosterone synthase (CYP11B2), including sex-SNP or SNP-SNP interactions. Eighty-eight tagSNPs were tested in 2872 white individuals in 809 pedigrees from the Victorian Family Heart Study using variance components models. Three SNPs (rs8075924 and rs4277404 at ACE and rs12721297 at AGTR1) were individually associated with lower systolic blood pressure with significant (P<0.00076) effect sizes ≈1.7 to 2.5 mm Hg. Sex-specific associations were seen for 3 SNPs in men (rs2468523 and rs2478544 at AGT and rs11658531 at ACE) and 1 SNP in women (rs12451328 at ACE). SNP-SNP interaction was suggested (P<0.005) for 14 SNP pairs, none of which had shown individual association with systolic blood pressure. Four SNP pairs were at the same gene (2 for REN, 1 for AGT, and 1 for AGTR1). The SNP rs3097 at CYP11B2 was represented...

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Genetic Variation in the Renin-Angiotensin System and Autonomic Nervous System Function in Young Healthy Japanese Subjects

Abstract: Cardiac autonomic function can be modulated by genetic variation in the RAS even in young and healthy states.

Cited by 22 publications

References 39 publications

C allele of angiotensin II type 1 receptor gene A1166C polymorphism affects plasma adiponectin concentrations in healthy young Japanese women

C allele of angiotensin II type 1 receptor gene A1166C polymorphism affects plasma adiponectin concentrations in healthy young Japanese women

Angiotensin II type 1 receptor polymorphisms and susceptibility to hypertension: A HuGE review

Familial Analysis of Epistatic and Sex-Dependent Association of Genes of the Renin–Angiotensin–Aldosterone System and Blood Pressure

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