A Prospective Evaluation of an Angiotensin-Converting–Enzyme Gene Polymorphism and the Risk of Ischemic Heart Disease

Lindpaintner, Klaus; Pfeffer, Marc A.; Kreutz, Reinhold; Stampfer, Meir J.; Grodstein, Francine; Lamotte, F; Buring, Julie E.; Hennekens, Charles H.

doi:10.1056/nejm199503163321103

Cited by 838 publications

(558 citation statements)

References 36 publications

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“…Another possibility is that the contribution of GNB3 gene to the pathogenesis of EH may be less significant than initially implied in the previous population studies, partly because of ethnicity-specific combination of genetic backgrounds and environmental factors. The frequency of the 825T allele in the present subjects was remarkably higher (50.1%) than that reported in Amerindians (26.5%) and western Europeans (29.6%), 32 but was similar to that described in Taiwan Han Chinese (54.3%), 29 northern Chinese (52%), 25 Canadian Oji-Cree (50.1%) 37 and Japanese populations (49%). 33 On the other hand, the frequency of the 825T allele in our population was much lower than that in Africans (79%), whereas it was slightly higher than the southern Chinese population (43.2%) reported by Siffert et al 37 As for the ACE I/D polymorphism, the D allele of the ACE gene is reportedly associated with the development of EH.…”

Section: Discussionsupporting

confidence: 72%

“…PCR profiling and genotyping of I/D polymorphisms were carried out as described by Rigat et al 28 To avoid mistyping of I/D heterozygotes as DD homozygotes, because of the preferential amplification of the D allele in heterozygous samples, all DD homozygous samples were subjected to an independent PCR amplification with a primer pair that identifies an insertion-specific sequence as reported previously. 29 Genotypes for the C825T polymorphism of the GNB3 gene were determined by PCR amplification followed by restriction digestion using BsaJI endonuclease (New England Biolabs, Beverly, MA, USA) as previously described, with minor modification. 21 Statistical analyses All data were presented as mean7s.d.…”

Section: Determination Of Genotypesmentioning

confidence: 99%

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Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans

et al. 2006

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Essential hypertension (EH) is considered a typical polygenic disease, so the evaluation of gene-gene interactions rather than the determination of single gene effects is crucial to understanding any genetic influences. The G-protein b3-subunit (GNB3) 825T allele, associated with enhanced G-protein signalling, is a strong candidate for interactions with polymorphisms, such as insertion/deletion (I/D) polymorphism of angiotensin I-converting enzyme (ACE) gene. We investigated whether there is an association between GNB3 C825T and ACE I/D polymorphisms for the development of EH. We carried out a case-control study of 688 hypertensive and 924 normotensive subjects recruited from South Korea. The GNB3 C825T and ACE I/D genotypes were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods, respectively. The distributions of alleles and genotypes for the GNB3 C825T and ACE I/D polymorphisms were not found to be significantly associated with hypertensive status in either males or females. Logistic regression analysis indicated that the GNB3 825T allele carriers were positively associated with EH in males (odds ratio (OR) for TT/CT, 1.459; 95% confidence interval (CI), 1.048-2.033, P ¼ 0.0255). In analysis of gene-gene interaction, we found that there was a significant interaction between the GNB3 825T and ACE D alleles (Po0.05). OR for EH was significantly higher in 825T allele carriers with ACE D allele (OR, 1.490; 95% CI, 1.117-1.987, P ¼ 0.0067). A significant interaction between the GNB3 825T and the ACE D alleles may contribute to the predisposing effect for the development of EH in Koreans.

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Section: Discussionsupporting

confidence: 72%

Section: Determination Of Genotypesmentioning

confidence: 99%

Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans

et al. 2006

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“…Oligonucleotide primers used to amplify the I/D region of the human ACE gene were as described by Lindpainter et al 15 Primers 5Ј GCCCTGCAGGTGTCTGCAGCATGT-3Ј (sense primer) and 5Ј GGATGGCTCTCCCCGCC TTGTCTC-3Ј (antisense primer) produced 319 and 597-bp amplicons for D and I alleles, respectively. Reactions were carried out in a total volume of 25 l containing 0.5 M primers, 2.0 mM deoxynucleotide triphosphate, 1.3 M Cl 2 Mg, 50 mM KCI, 10 mM tris HCI, pH 8.4, 0.1%, Triton X-100, 0.5 units of Taq polymerase and 100 g of human genomic DNA.…”

Section: Methodsmentioning

confidence: 99%

“…The amplification products (D and I alleles) were analysed using 2% agarose electrophoresis. Because the D allele in heterozygous samples is preferentially amplified 15 , each sample found to have the DD genotype was subjected to a second independent PCR amplification, with a primer pair that recognised an insertion-specific sequence. The primers were 5Ј TGGGACCACAGCGCCCGCCACTAC-3Ј (sense primer) and 5ЈTCGCCAGCCCTCCCATGCCCATAA-3Ј (antisense primer).…”

Section: Methodsmentioning

confidence: 99%

Angiotensin-converting enzyme (ACE) gene polymorphisms, serum ACE activity and blood pressure in a Spanish-Mediterranean population

et al. 2000

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Angiotensin-converting enzyme (ACE) levels and ACE gene polymorphisms have been related with hypertension but with contradictory results between populations. We have investigated the association among the allelic distribution of the insertion-deletion (I/D) polymorphism of the ACE gene, identified by polymerase chain reaction (PCR), serum ACE activity determined by spectrophotometry, and the blood pressure (BP), in a Mediterranean population in the southwest of Europe. A total of 1322 randomised individuals were analysed, and a comparative study was conducted analysing 205 indi-

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“…After this, however, further important conflicting evidence came from the Physicians' Health Study [51]. This large prospective study, larger than any of the previous ones, did not confirm any role of the ACE genotype as a marker for either myocardial infarction or ischaemic heart disease.…”

Section: The Insertion/deletion (I/d) Polymorphism Of the Ace Gene Anmentioning

confidence: 66%

Aspects of gene polymorphisms in cardiovascular disease: the renin‐angiotensin system

Carluccio

Soccio

Caterina

2001

Eur J Clin Investigation

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The renin-angiotensin system (RAS) plays a central role in cardiovascular homeostasis. Angiotensin is the key peptide of the RAS, and exerts its influence on the heart and blood vessels both through its haemodynamic effects (via its influence on after-load and pre-load and determining coronary vasoconstriction) and through its direct cellular effects (via its actions on cell proliferation). Numerous studies in the past 10 years have demonstrated that the pharmacological inhibition of angiotensin converting enzyme (ACE), one of the two critical enzymes of the RAS, improves the outcome in patients with several cardiovascular disorders (hypertension, heart failure, ischaemic heart disease). These studies suggest a role of the RAS as a major determinant of cardiovascular risk. Recent data suggest that genetics may in turn contribute to modulating the effects of angiotensin on coronary vascular biology and ischaemia. This paper reviews the physiologic characteristics of the RAS and recent research developments related to angiotensin cell biology and pathobiology in heart disease. In particular, this review will cover the genetic aspects of RAS and their implications in cardiovascular disease.

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A Prospective Evaluation of an Angiotensin-Converting–Enzyme Gene Polymorphism and the Risk of Ischemic Heart Disease

Abstract: In a large, prospectively followed population of U.S. male physicians, the presence of the D allele of the ACE gene conferred no appreciable increase in the risk of ischemic heart disease or myocardial infarction.

Cited by 838 publications

References 36 publications

Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans

Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans

Angiotensin-converting enzyme (ACE) gene polymorphisms, serum ACE activity and blood pressure in a Spanish-Mediterranean population

Aspects of gene polymorphisms in cardiovascular disease: the renin‐angiotensin system

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