Interaction between the Gly460Trp α-adducin gene variant and diuretics on the risk of myocardial infarction

Wijer, Diane B M A Van Wieren-De; Zee, Anke‐Hilse Maitland‐van der; Boer, Anthonius de; Kroon, Abraham A.; Leeuw, Peter W. de; Schiffers, P. M. H.; Janssen, Rob; Psaty, Bruce M.; Duijn, Cornelia M. van; Stricker, Bruno H. Ch.; Klungel, Olaf H.

doi:10.1097/hjh.0b013e328317a74d

Cited by 31 publications

(19 citation statements)

References 31 publications

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“…Further, a recent analysis in the Rotterdam study demonstrated an association of the Gly460Trp allele with higher risk of stroke (HR = 1.22; 95% CI, 1.02 to 1.45) and myocardial infarction (HR=1.33; 95% CI, 1.05 to 1.69). However, a recent study did not find an interaction effect of the Gly460Trp variant with thiazide diuretics treatment in either the wild-type or the minor allele carriers [45].…”

Section: Future Studies and Pharmacogenomicsmentioning

confidence: 98%

Genome-Wide Association Studies of Hypertension: Have They Been Fruitful?

Rafiq

Anand

Roberts

2010

J. of Cardiovasc. Trans. Res.

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Over the last two decades candidate gene association studies and genome-wide linkage scans have met with little success in characterizing risk variants for hypertension. Several factors could be responsible for the relative lack of success, although our understanding of the genetics has evolved to support the belief that there are multiple common risk variants, which are associated with hypertension with modest effect sizes. Genome-wide association studies (GWAS) have successfully identified risk loci for several complex polygenic disease states. Until recently, the productivity of GWAS with respect to identifying risk loci for hypertension was limited. In this paper we describe the recent success of GWAS of hypertension in identifying over a dozen loci associated with essential hypertension. We will review these findings, and place these results in the context of the future potential of pharmocogenetics of hypertension.

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Section: Future Studies and Pharmacogenomicsmentioning

confidence: 98%

Genome-Wide Association Studies of Hypertension: Have They Been Fruitful?

Rafiq

Anand

Roberts

2010

J. of Cardiovasc. Trans. Res.

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“…Ptsay et al demonstrated that the minor allele carriers of the ADD1gene taking thiazide diuretic therapy were at lower risk of suffering from myocardial infarction or stroke compared to wild-type patients, suggesting that in the presence of constitutive enhanced tubular sodium reabsorption, drugs such as diuretics should trigger less counter-regulatory mechanisms, thus yielding a more beneficial therapeutic effect [203]. However, again these findings were not replicated in larger controlled clinical trials [204][205][206]. Interestingly, ADD1 Gly460Trp, WNK1, and NEDD4L (rs4149601) specific haplotypes were found to significantly interact to control systolic blood pressure after thiazide diuretic therapy, suggesting the need to investigate the gene-gene interactions to detect significant pharmacogenetics effects [178,207].…”

Section: Pharmacogenetics and Pharmacogenomics Of Antihypertensive Drugsmentioning

confidence: 89%

Susceptibility Genes in Hypertension

Armani¹,

Botto

Andreassi

2011

CPD

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Hypertension is a complex, multifactorial disease; genetic factors represent one third to half of the inter-individual variability of blood pressure values. Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Recent advances in molecular biology have revealed the pathogenesis of hypertension in many of these conditions. Remarkably, the mechanism in every case has proved to be upregulation of sodium Na reabsorption in the distal nephron, with accompanying expansion of extracellular volume. On the contrary in the essential hypertension the underlying pathogenetic mechanism is more complex because of interplay between several 'risk' genes and environmental factors. It is assumed that blood pressure is under the control of a large number of genes each of which has only relatively mild effects. It has therefore been difficult to discover the genes that contribute to blood pressure variation using traditional approaches including candidate gene studies and linkage studies. Recent development of genotyping technology made large scale genome-wide association studies possible. This approach and the study of monogenic forms of hypertension has led to the discovery of novel and robust candidate genes for human essential hypertension, many of which require functional analysis in experimental models. This review summarizes the current findings for candidate genes associated with blood pressure and focuses on recent advances and future potential of pharmacogenetics of hypertension, with the intent to clarify what amount of these investments in basic science research will be delivered into benefits to patients.

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“…Parallel studies in a hypertensive rat model and in human patients have indicated that the Gly460Trp polymorphism is associated with alterations in ADD1 function that may affect constitutive tubular sodium reabsorption [141,142]. While initially diuretic therapy in carriers of the ADD1 460Trp variant was associated with a positive response to treatment, several recent studies have failed to replicate this finding [56,117,143,144]. This controversy has been proposed to be attributable to differences in environmental factors, ethnic background and lifestyle of patients across different studies [135,144].…”

Section: Add1 Polymorphisms and Diuretic Drug Responsementioning

confidence: 94%

“…While initially diuretic therapy in carriers of the ADD1 460Trp variant was associated with a positive response to treatment, several recent studies have failed to replicate this finding [56,117,143,144]. This controversy has been proposed to be attributable to differences in environmental factors, ethnic background and lifestyle of patients across different studies [135,144]. Of all genes assessed to date, ADD1 is the most relevant in response to diuretic treatment however, additional players may surface through future large scale pharmacogenetic studies.…”

Section: Add1 Polymorphisms and Diuretic Drug Responsementioning

confidence: 94%

Pharmacogenetically Tailored Treatments for Heart Disease

Vafiadaki¹,

Arvanitis²,

Kranias³

et al. 2010

CPD

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Heart disease represents the primary cause of death worldwide, with mortality rates being predicted to remain constant within the next couple of decades. Cardiac disease treatment currently includes the administration of drugs, predominantly aiming at improving heart performance, through controlling heart rhythm, blood pressure, as well as reducing cholesterol and blood clotting. Despite, however, the medical advances that have lead towards a better understanding of heart disease pathophysiology and the development of new therapeutic approaches, the degree of success of the available drug therapies varies among patients. The existence of polymorphisms in a number of genes has been shown to result in differences in pharmacokinetics, pharmacodynamics and drug metabolism and have therefore been associated with response to drug treatment. The occurrence of adverse drug reactions that may lead to drug-induced toxicity represents another factor influencing outcome of therapeutic treatment. While the influence of genetic polymorphisms in patient's response to heart disease drugs is being unveiled, the rapidly evolving field of pharmacogenetics is promising to aid clinicians in choosing the best suited drug/dose for each patient and the pharmaceutical companies in the design of better targeted, more effective new chemical compounds. In the near future individualized, targeted therapy will become part of clinical care routine maximizing patient therapeutic benefits and minimizing risks of adverse effects.

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Interaction between the Gly460Trp α-adducin gene variant and diuretics on the risk of myocardial infarction

Abstract: This study suggests that the alpha-adducin gene does not play an important role in modifying the risk of nonfatal MI associated with the use of thiazide diuretics.

Cited by 31 publications

References 31 publications

Genome-Wide Association Studies of Hypertension: Have They Been Fruitful?

Genome-Wide Association Studies of Hypertension: Have They Been Fruitful?

Susceptibility Genes in Hypertension

Pharmacogenetically Tailored Treatments for Heart Disease

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