Angiotensin-converting enzyme 2 A1075G polymorphism is associated with survival in an acute coronary syndromes cohort

Palmer, Barry R.; Jarvis, Martin D.; Pilbrow, Anna P.; Ellis, Katrina L.; Frampton, Chris; Skelton, Lorraine; Yandle, Tim G.; Doughty, Rob; Whalley, Gillian A.; Ellis, Chris; Troughton, Richard W.; Richards, A. Mark; Cameron, Vicky A.

doi:10.1016/j.ahj.2008.06.013

Cited by 25 publications

(29 citation statements)

References 31 publications

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“…However this does not help to explain why the study by Palmer et al 21 found that a SNP in ACE2 was associated with the risk of CVD mortality in men but to a lesser degree in women. This apparent contradiction may be accounted for by differing effects of the two SNPs on the ACE2 protein, which are currently unknown.…”

Section: Discussionmentioning

confidence: 88%

A polymorphism in ACE2 is associated with a lower risk for fatal cardiovascular events in females: the MORGAM project

Vangjeli

Trégouët

Shields

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Angiotensin II, a vasoconstrictor and the main effector molecule of the renin-angiotensin system, is known to influence inflammation, thrombosis, low-density lipoprotein oxidation and growth factors, all of which contribute to cardiovascular disease. The associations of polymorphisms in the angiotensin-converting enzyme 2 (ACE2) gene with cardiovascular risk have not been fully determined. Single nucleotide polymorphisms (SNPs) in ACE2 were genotyped in participants of the prospective MORGAM study (n = 5092) from five cohorts: ATBC, FINRISK, Northern Sweden, PRIME/Belfast and PRIME/France. Using a case-cohort design, associations were sought between SNPs and haplotypes with cardiovascular events during follow-up (Cox proportional hazards model). The comparison group were a subset of all MORGAM participants who were selected to ensure similar age and sex distributions among the cases and controls. The A allele of the rs2285666 SNP (HR = 0.3, p = 0.04) was significantly associated with the risk of cardiovascular death in female subjects. These findings complement those found in other studies of SNPs in the ACE2 gene in relation to cardiovascular disease risk. As females carry two copies of the ACE2 gene, and given its plausible biological role in cardiovascular disease risk, further studies of ACE2 should be prioritized.

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Section: Discussionmentioning

confidence: 88%

A polymorphism in ACE2 is associated with a lower risk for fatal cardiovascular events in females: the MORGAM project

Vangjeli

Trégouët

Shields

et al. 2011

J Renin Angiotensin Aldosterone Syst

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“…Patients attended follow-up clinics 3–5 months and 12–14 months post-onset of ACS and participants completed questionnaires at two years and three years post-discharge. Standardized transthoracic echocardiography was performed using a GE Vivid 3 ultrasound system (GE Medical Systems, Auckland) at Christchurch Hospital and an ATL HDI 5000 (Philips Healthcare, Sydney) at Auckland City Hospital as described previously [5]. The New Zealand Multi-Region Ethics Committee approved the study.…”

Section: Methodsmentioning

confidence: 99%

“…Extraction of genomic DNA for genotyping was performed as described previously [5]. DNA samples were genotyped for the rs6922269 polymorphism in 10 µL reaction volumes using allele-specific TaqMan genotyping probes (Applied Biosystems, USA), including 1× Thermo qPCR ROX Mix (Thermo, UK) and 100 ng of genomic DNA in a Roche LC480 (Roche Diagnostics, Auckland).…”

Section: Methodsmentioning

confidence: 99%

“…Genetic markers offer the promise of identifying individual patients at increased risks of early disease-onset, or worse prognosis, and who may benefit from additional screening and early intervention. Genetic polymorphisms have been associated with increased risk for ACS [1], [2], [3], but the number of reports investigating genetic association with clinical outcome following specific ACS events is comparatively few [4], [5], [6].…”

Section: Introductionmentioning

confidence: 99%

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Genetic Polymorphism rs6922269 in the MTHFD1L Gene Is Associated with Survival and Baseline Active Vitamin B12 Levels in Post-Acute Coronary Syndromes Patients

et al. 2014

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Background and AimsThe methylene-tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L) gene is involved in mitochondrial tetrahydrofolate metabolism. Polymorphisms in MTHFD1L, including rs6922269, have been implicated in risk for coronary artery disease (CAD). We investigated the association between rs6922269 and known metabolic risk factors and survival in two independent cohorts of coronary heart disease patients.Methods and ResultsDNA and plasma from 1940 patients with acute coronary syndromes were collected a median of 32 days after index hospital admission (Coronary Disease Cohort Study, CDCS). Samples from a validation cohort of 842 patients post-myocardial infarction (PMI) were taken 24–96 hours after hospitalization. DNA samples were genotyped for rs6922269, using a TaqMan assay. Homocysteine and active vitamin B12 were measured by immunoassay in baseline CDCS plasma samples, but not PMI plasma. All cause mortality was documented over follow-up of 4.1 (CDCS) and 8.8 (PMI) years, respectively. rs6922269 genotype frequencies were AA n = 135, 7.0%; GA n = 785, 40.5% and GG n = 1020, 52.5% in the CDCS and similar in the PMI cohort. CDCS patients with AA genotype for rs6922269 had lower levels of co-variate adjusted baseline plasma active vitamin B12 (p = 0.017) and poorer survival than patients with GG or GA genotype (mortality: AA 19.6%, GA 12.0%, GG 11.6%; p = 0.007). In multivariate analysis, rs6922269 genotype predicted survival, independent of established covariate predictors (p = 0.03). However the association between genotype and survival was not validated in the PMI cohort.Conclusion MTHFD1L rs6922269 genotype is associated with active vitamin B12 levels at baseline and may be a marker of prognostic risk in patients with established coronary heart disease.

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“…Completion of the Human Genome Project has opened a new window to investigate genetic means for the treatment of hypertension through overexpression of ACE2 gene (Ferreira & Raizada, 2008; Katovich et al, 2005). Polymorphisms of the ACE2 gene have been associated with essential hypertension (Fan et al, 2007; Huang et al, 2006; Liu et al, 2005; Mo et al, 2010; Niu et al, 2007; Yi et al, 2006), LV hypertrophy, coronary artery disease, and myocardial infarction (Lieb et al, 2006; Palmer et al, 2008; Sotoodehnia et al, 2009; Wang et al, 2008b; Yan et al, 2008; Yang et al, 2006). …”

Section: Angiotensin-converting Enzyme 2 As a Component Of The Anmentioning

confidence: 99%

Advances in the Renin Angiotensin System

Ferrario

Ahmad²,

Joyner³

et al. 2010

Cardiovascular Pharmacology - Heart and Circulation

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The contribution of the renin angiotensin system to physiology and pathology is undergoing a rapid reconsideration of its mechanisms from emerging new concepts implicating angiotensin-converting enzyme 2 and angiotensin-(1–7) as new elements negatively influencing the vasoconstrictor, trophic, and pro-inflammatory actions of angiotensin II. This component of the system acts to oppose the vasoconstrictor and proliferative effects on angiotensin II through signaling mechanisms mediated by the mas receptor. In addition, a reduced expression of the vasodepressor axis composed by angiotensin-converting enzyme 2 and angiotensin-(1–7) may contribute to the expression of essential hypertension, the remodeling of heart and renal function associated with this disease, and even the physiology of pregnancy and the development of eclampsia.

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Angiotensin-converting enzyme 2 A1075G polymorphism is associated with survival in an acute coronary syndromes cohort

Cited by 25 publications

References 31 publications

A polymorphism in ACE2 is associated with a lower risk for fatal cardiovascular events in females: the MORGAM project

A polymorphism in ACE2 is associated with a lower risk for fatal cardiovascular events in females: the MORGAM project

Genetic Polymorphism rs6922269 in the MTHFD1L Gene Is Associated with Survival and Baseline Active Vitamin B12 Levels in Post-Acute Coronary Syndromes Patients

Advances in the Renin Angiotensin System

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