Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls

Keavney, Bernard; McKenzie, Colin A.; Parish, Sarah; Palmer, Amy; Clark, SJ; Youngman, Linda; Délépine, Marc; Lathrop, Mark; Pető, Richárd; Collins, Richard

doi:10.1016/s0140-6736(99)07192-5

Cited by 116 publications

(113 citation statements)

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“…The unbalanced vascular tones increase the arterial stiffness and, consequently, increase the risk of development of lower extremity arterial disease (LEAD) or other vascular diseases. Previous reports on the association of essential hypertension [12][13][14] and cardiovascular diseases 15,16 with G-6A, T174M, M235T and ACE are inconsistent, possibly due to small sample size or unrecognized confounders or effect modifiers. In addition, the relationship between RAS genes and LEAD in Europeans and Asians [17][18][19] is also inconsistent.…”

Section: Introductionmentioning

confidence: 94%

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study

Nicklas

Pahor

et al. 2007

J Hum Hypertens

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The role of renin-angiotensin system (RAS) genes on the risk of lower extremity arterial disease (LEAD) in elderly people remains unclear. We assessed the relationship of genetic polymorphisms in RAS: G-6A, T174M and M235T of the angiotensinogen (AGT) gene, and the angiotensin-converting enzyme insertion/deletion (ACE_I/D) variant to the risk of LEAD in the Health, Aging and Body Composition (Health ABC) Study. This analysis included 1228 black and 1306 white men and women whose age ranged between 70 and 79 years at the study enrollment. LEAD was defined as ankle-arm index (AAI) o0.9. Genotype-phenotype associations were estimated by regression analyses with and without adjustment for established cardiovascular disease (CVD) risk factors. The proportion of LEAD was significantly higher in black (21.1%) than that in white elderly people (10.1%, Po0.0001). The distribution of AGT polymorphisms was also significantly different between black and white participants. There was no statistically significant association between the selected RAS genetic variants and LEAD after adjustment for age, antihypertensive medications, lipid-lowering medication, pack-year smoking, body mass index, low-density lipoprotein cholesterol, and prevalent diabetes and coronary heart disease. However, A-T haplotype of G-6A and M235T interacting with homozygous ACE_II (b ¼ À1.07, P ¼ 0.006) and with ACE inhibitors (b ¼ À1.03, P ¼ 0.01) significantly decreased the risk of LEAD in white but not in black participants after adjustment for the selected CVD risk factors. In conclusion, the study observed a gene-gene and gene-drug interaction for LEAD in the white elderly.

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Section: Introductionmentioning

confidence: 94%

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study

Nicklas

Pahor

et al. 2007

J Hum Hypertens

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“…Likewise, available evidence suggest that the D allele causes a modest-and most likely irrelevant-increase in the risk for other cardiovascular and renal diseases (Cambien et al 1992;Schunkert et al 1994;Iwai et al 1994;Pontremoli et al 1996;Fernandez-Llama et al 1998). For these entities, meta-analyses revealed odds ratios for carriers of the DD genotype ranging from 1.04-1.43 for myocardial infarction (Agerholm-Larsen et al 2000;Keavney et al 2000) and from 1.28-1.56 (Staessen et al 1997;Ng et al 2005) for diabetic nephropathy.…”

Section: Polymorphisms In the Angiotensin Converting Enzymementioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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“…Several studies on the association of ACE I/D dimorphism and the risk of developing CVDs, such as essential hypertension (EH) [9][10][11][12][13][14][15][16][17][18] and myocardial infarction (MI), [19][20][21][22][23][24][25][26][27][28] have generated inconsistent information. This instigated a search for new polymorphisms in the ACE gene to identify better markers or actual functional variants.…”

Section: Introductionmentioning

confidence: 99%

Association of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with essential hypertension

et al. 2003

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Although the angiotensin converting enzyme (ACE) is a strong candidate gene for hypertension, the extensively studied insertion-deletion dimorphism in intron 16 was not found to be associated with it. Several new polymorphisms in the ACE gene were identified, among which a dimorphism in exon 17, ACE G2350A, has a significant effect on plasma ACE concentrations. To assess the value of genotyping the ACE G2350A dimorphism in a genetically homogeneous population, we carried out a retrospective, case-control study of dimorphism G2350A for a putative association with essential hypertension (EH) in a Gulf population (Emirati)-an ethnic group characterized by no alcohol intake and no cigarette smoking. We investigated a sample population of 254 Emirati, comprising 136 normotensive controls, and 118 patients with clinical diagnoses of EH. ACE G2350A alleles were visualized by assays based on polymerase chain reaction and restriction endonuclease analysis. The ACE G2350A dimorphism showed an association with EH (v 2 ¼ 6.71, 2 df, P ¼ 0.05). Further analysis revealed that the ACE G/G 2350 genotype was positively associated (OR ¼ 1.06-3.07, P ¼ 0.02) with EH. This is the first association study of the ACE G2350A dimorphism with EH, and the positive result might indicate that ACE could be a QTL for EH as originally thought.

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Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls

Cited by 116 publications

References 0 publications

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study

Genetics of arterial hypertension and hypotension

Association of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with essential hypertension

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