Variants of the CYP11B2 gene predict response to therapy with candesartan

Ortlepp, Jan R.; Hanrath, Peter; Mevissen, Vera; Kiel, Gerhard; Borggrefe, Martin; Hoffmann, Rainer

doi:10.1016/s0014-2999(02)01766-1

Cited by 39 publications

(23 citation statements)

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“…Results have, however, been conflicting, with the blood pressure-reducing effects being most pronounced in TT-carrying hypertensive patients in one study [31] and CCindividuals in another [33]. As blood pressure is a major risk factor for progressive renal failure in diabetic patients, we measured the impact of the − 344T/C polymorphism on the long-term decline in glomerular filtration rate in ACE-inhibitor treated patients with diabetic nephropathy.…”

Section: Discussionmentioning

confidence: 99%

Aldosterone synthase (CYP11B2) −344T/C polymorphism is not associated with the initiation and progression of diabetic nephropathy in Caucasian Type 1 diabetic patients

Lajer¹,

Schjoedt²,

Jacobsen³

et al. 2006

Diabetic Medicine

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Section: Discussionmentioning

confidence: 99%

Aldosterone synthase (CYP11B2) −344T/C polymorphism is not associated with the initiation and progression of diabetic nephropathy in Caucasian Type 1 diabetic patients

Lajer¹,

Schjoedt²,

Jacobsen³

et al. 2006

Diabetic Medicine

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“…In one study, losartan and the C allele of AT 1 R A1166C interacted favorably to effect a greater reduction in mean blood pressure [Miller et al, 2000]. In another study, candesartan and the C allele of CYP11B2 À344 T/C interacted favorably for a greater reduction in DBP [Ortlepp et al, 2002]. In the same study, candesartan showed no differential response to ACE I/D genotypes.…”

Section: Angiotensin II Blockersmentioning

confidence: 95%

Pharmacogenetics of antihypertensive treatment

Arnett

Claas

2004

Drug Development Research

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Hypertension is a common disorder associated with increased cardiovascular morbidity and mortality. Unfortunately, in the United States, only about one third of those who are aware of their hypertensive status successfully control their blood pressure. One reason for this is the variable and unpredictable response individuals have to pharmacologic treatment. Clinicians often resort to a trial-anderror approach to match patients with effective drug treatment. It is the goal of hypertension pharmacogenetics to apply knowledge of genetic predictors of treatment response to drugs that lower blood pressure and to translate this knowledge into clinical practice. To date, more than 30 studies have investigated associations between specific genetic polymorphisms and response to particular antihypertensive drugs. Angiotensin-converting enzyme inhibitors have been most frequently studied, followed by diuretics, beta-blockers, angiotensin II blockers, adrenergic alpha-agonists, and calcium channel blockers. Renin-angiotensin-aldosterone system genes have been the most widely studied, with the angiotensinconverting enzyme I/D variant being typed in about one third of all hypertension pharmacogenetic studies to date. In a number of cases, significant and potentially promising associations between genes and drug treatments have been reported. However, taken in sum, the literature suggests that the path from genedrug-outcome association studies to clinically useful knowledge may be neither short nor direct. In the future, carefully designed studies must acknowledge that hypertension is caused by multiple genes and environmental factors that act in concert. These considerations, along with a better understanding of the complexities of the biology of hypertension, open the next set of opportunities for hypertension pharmacogenetics research. Drug Dev.

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“…Few studies investigated the effect of proteins that are involved in the absorption, transportation, and metabolisms of ACE inhibitors or ARBs such as the CYP11B2 promoter polymorphism (Ortlepp et al [17]). Such a study emphasizes the importance of genome-wide approaches instead of limited genes to evaluate the possibility of geneegene interaction.…”

Section: Candidate Genes Vs Genome-wide Strategiesmentioning

confidence: 99%

“…For example, in one study (Ortlepp et al [17]) a small portion of patients who participated in a phase III randomized clinical trial were selected for a genomics study. In this study obtaining a written informed consent from the patient was a determinant criterion for inclusion.…”

Section: Biases Driven From Patient Selection and Indicationmentioning

confidence: 99%

“…Some studies combined different brands of ACE inhibitors with different pharmacokinetics and pharmacodynamics properties as one group for association analysis (Hingorani et al [20], Ortlepp et al [17]). Different pharmacokinetics and pharmacodynamics properties may produce various degrees of the effect for geneedrug interactions resulting in a biased analysis.…”

Section: Biases Driven From Combining Different Therapeuticsmentioning

confidence: 99%

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