Genetic polymorphisms in the renin–angiotensin system: relevance for susceptibility to cardiovascular disease

Wang, Ji‐Guang; Staessen, Jan A.

doi:10.1016/s0014-2999(00)00822-0

Cited by 151 publications

(116 citation statements)

References 114 publications

(147 reference statements)

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“…25,26 Furthermore, the previous study by Perkins et al 14 showed that in 63 HCM patients with single (different) mutations in the MYBPC3 gene, the DD-ACE genotype was a significant pro-LVH modifier, being associated with an increased left ventricular wall thickness, and with extreme IVS thickness (430 mm). Similar findings were reported by Ortlepp et al 13 in 26 c.2373dupG mutation carriers from one family.…”

Section: Discussionmentioning

confidence: 97%

The role of renin–angiotensin–aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

et al. 2012

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The phenotypic variability of hypertrophic cardiomyopathy (HCM) in patients with identical pathogenic mutations suggests additional modifiers. In view of the regulatory role in cardiac function, blood pressure, and electrolyte homeostasis, polymorphisms in the renin-angiotensin-aldosterone system (RAAS) are candidates for modifying phenotypic expression. In order to investigate whether RAAS polymorphisms modulate HCM phenotype, we selected a large cohort of carriers of one of the three functionally equivalent truncating mutations in the MYBPC3 gene. Family-based association analysis was performed to analyze the effects of five candidate RAAS polymorphisms (ACE, rs4646994; AGTR1, rs5186; CMA, rs1800875; AGT, rs699; CYP11B2, rs1799998) in 368 subjects carrying one of the three mutations in the MYBPC3 gene. Interventricular septum (IVS) thickness and Wigle score were assessed by 2D-echocardiography. SNPs in the RAAS system were analyzed separately and combined as a pro-left ventricular hypertrophy (LVH) score for effects on the HCM phenotype. Analyzing the five polymorphisms separately for effects on IVS thickness and Wigle score detected two modest associations. Carriers of the CC genotype in the AGT gene had less pronounced IVS thickness compared with CT and TT genotype carriers. The DD polymorphism in the ACE gene was associated with a high Wigle score (P ¼ 0.01). No association was detected between the pro-LVH score and IVS thickness or Wigle score. In conclusion, in contrast to previous studies, in our large study population of HCM patients with functionally equivalent mutations in the MYBPC3 gene we did not find major effects of genetic variation within the genes of the RAAS system on phenotypic expression of HCM.

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Section: Discussionmentioning

confidence: 97%

The role of renin–angiotensin–aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

et al. 2012

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“…[17][18][19] Conversely, testosterone was shown to increase secretion of such vasoconstrictors as endothelin and stimulates the renin-angiotensin-aldosterone system, leading to inadequate sodium excretion in the setting of increased arterial blood pressure. 18,19 Genetic variability related to the renin-angiotensin-aldosterone system and/or the α-adrenergic receptor also was linked in population-based studies to sex differences in blood pressure in both African Americans 20 and whites. 21 However, a primary biological explanation for sex differences in hypertension control would suggest persistently increased blood pressures for both African American and white men relative to women.…”

Section: Discussionmentioning

confidence: 99%

Race and Sex Differences in Hypertension Control in CKD: Results From the Kidney Early Evaluation Program (KEEP)

Duru¹,

Li²,

Jurkovitz

et al. 2008

American Journal of Kidney Diseases

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“…2 Many reports suggest that the renin-angiotensin system (RAS) has an important role in the development of CVD, including contributions from the vasoactive peptide angiotensin II-produced from angiotensinogen (AGT) by renin and angiotensin-converting enzyme (ACE)-and its receptor, angiotensin II type 1 receptor (AT1R). [3][4][5] RAS-component gene polymorphisms such as the M235T single nucleotide polymorphism (SNP) in AGT, the insertion (I)/deletion (D) polymorphisms in ACE, and the A1166C SNP in AT1R have been reported from various laboratories, including our group. Subjects with the TT AGT genotype have 10-20% higher plasma AGT concentrations, 6 and subjects with the ACE D allele exhibit higher levels of serum and tissue ACE.…”

Section: Introductionmentioning

confidence: 95%

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

et al. 2011

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The renin-angiotensin system (RAS) adversely affects stroke and cardiovascular disease; polymorphisms in genes involved in this system are associated with cardiovascular disease. The aim of the present study was to confirm the genetic risk of these polymorphisms for stroke and cardiovascular events in a cohort study of 515 hypertensive patients in Japan (follow-up period 90.6±30.2 months). The insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE), the M235T amino acid change in angiotensinogen, and the A1166C polymorphism in angiotensin II type 1 receptor were determined by TaqMan PCR. In Kaplan-Meier analyses, the ACE I/D polymorphism was a risk factor for cerebro-cardiovascular events, especially cardiovascular events (Po0.0001), and the M235T mutation was a risk factor for cardiovascular events (Po0.0105). The cumulative rates of cerebro-cardiovascular end points for the ACE polymorphism were 10.6, 16.4 and 42.2% for the II (n¼207), ID (n¼244) and DD (n¼64) genotype carriers, respectively (Po0.0001). Cox's proportional hazard models revealed that the ACE DD genotype was a risk factor for cerebro-cardiovascular and cardiovascular events (after adjusting for common risk factors), anti-hypertensive treatment and RAS inhibition (Po0.0001). Moreover, after adjustment for the common risk factors left ventricular hypertrophy and previous myocardial infarction/stroke, these phenomena were preserved. Thus, the DD genotype of ACE may be a genetic risk factor for cerebro-cardiovascular disease, especially cardiovascular events, in hypertensive patients in Japan.

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Genetic polymorphisms in the renin–angiotensin system: relevance for susceptibility to cardiovascular disease

Cited by 151 publications

References 114 publications

The role of renin–angiotensin–aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

The role of renin–angiotensin–aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

Race and Sex Differences in Hypertension Control in CKD: Results From the Kidney Early Evaluation Program (KEEP)

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

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