Genetic Variants Associated With Uncontrolled Blood Pressure on Thiazide Diuretic/β‐Blocker Combination Therapy in the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) and INVEST (International Verapamil‐SR Trandolapril Study) Trials

Magvanjav, Oyunbileg; Gong, Yan; McDonough, Caitrin W.; Chapman, Arlene B.; Turner, Stephen T.; Gums, John G.; Bailey, Kent R.; Boerwinkle, Eric; Beitelshees, Amber L.; Tanaka, Toshihiro; Kubo, Michiaki; Pepine, Carl J.; Cooper‐DeHoff, Rhonda M.

doi:10.1161/jaha.117.006522

Cited by 19 publications

(21 citation statements)

References 65 publications

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“…Consistently, these findings were replicated in an independent cohort treated with the thiazide diuretic chlorthalidone, thus validating the associations 42. Also employing a GWAS approach, Magvanjav et al found that the SNP rs261316 in the ALDH1A2 gene was associated with uncontrolled blood pressure following treatment with a thiazide diuretic/β-blocker combination in white participants of the PEAR study 43. These findings were further validated in a replication study including subjects from INVEST study 43.…”

Section: Diureticsmentioning

confidence: 66%

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Oliveira-Paula

Pereira

Tanus‐Santos

et al. 2019

PGPM

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Hypertension is a multifactorial disease that affects approximately one billion subjects worldwide and is a major risk factor associated with cardiovascular events, including coronary heart disease and cerebrovascular accidents. Therefore, adequate blood pressure control is important to prevent these events, reducing premature mortality and disability. However, only one third of patients have the effective control of blood pressure, despite several classes of antihypertensive drugs available. These disappointing outcomes may be at least in part explained by interpatient variability in drug response due to genetic polymorphisms. To address the effects of genetic polymorphisms on blood pressure responses to the antihypertensive drug classes, studies have applied candidate genes and genome wide approaches. More recently, a third approach that considers gene-gene interactions has also been applied in hypertension pharmacogenomics. In this article, we carried out a comprehensive review of recent findings on the pharmacogenomics of antihypertensive drugs, including diuretics, β-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and calcium channel blockers. We also discuss the limitations and inconsistences that have been found in hypertension pharmacogenomics and the challenges to implement this valuable approach in clinical practice.

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Section: Diureticsmentioning

confidence: 66%

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Oliveira-Paula

Pereira

Tanus‐Santos

et al. 2019

PGPM

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“…According to a recent review by Thies et al, there are not enough studies to draw substantial conclusions on the effects of lycopene on blood pressure [ 39 ]. Interestingly, the strong genetic correlation suggesting shared genetic factors affecting both lycopene concentrations and DBP may be plausible since SETD7 has been associated with both traits [ 15 , 61 ]. Indeed, a genetic variant (rs7680948) within SETD7 , encoding for SET domain containing lysine methyltransferase 7, was associated with serum lycopene concentrations in Amish adults [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, a genetic variant (rs7680948) within SETD7 , encoding for SET domain containing lysine methyltransferase 7, was associated with serum lycopene concentrations in Amish adults [ 15 ]. SETD7 was also associated with DBP response and may play a role in high glucose-induced vascular dysfunction [ 61 , 62 ]. Genetic variants and changes in expression of genes involved in lycopene absorption and metabolism may also impact CM risk factors including blood pressure but this area still needs to be further studied [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic and Common Environmental Contributions to Familial Resemblances in Plasma Carotenoid Concentrations in Healthy Families

et al. 2018

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Carotenoids have shown an interindividual variability that may be due to genetic factors. The only study that has reported heritability of serum α- and β-carotene has not considered the environmental component. This study aimed to estimate the contribution of both genetic and common environmental effects to the variance of carotenoid concentrations and to test whether their phenotypic correlations with cardiometabolic risk factors are explained by shared genetic and environmental effects. Plasma carotenoid concentrations (α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene, zeaxanthin, and total carotenoids) of 48 healthy subjects were measured. Heritability estimates of carotenoid concentrations were calculated using the variance component method. Lutein and lycopene showed a significant familial effect (p = 6 × 10−6 and 0.0043, respectively). Maximal heritability, genetic heritability, and common environmental effect were computed for lutein (88.3%, 43.8%, and 44.5%, respectively) and lycopene (45.2%, 0%, and 45.2%, respectively). Significant phenotypic correlations between carotenoid concentrations and cardiometabolic risk factors were obtained for β-cryptoxanthin, lycopene, and zeaxanthin. Familial resemblances in lycopene concentrations were mainly attributable to common environmental effects, while for lutein concentrations they were attributable to genetic and common environmental effects. Common genetic and environmental factors may influence carotenoids and cardiometabolic risk factors, but further studies are needed to better understand the potential impact on disease development.

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“…The authors suggested that two other family members of the ADH gene ( ALDH1A2 and ALDH7 ) are related to the presence of hypertension in African Americans, while ALDH2 was associated with BP control in an East Asian population [ 7 , 99 , 100 ]. A GWAS analysis found a relationship between the SNP rs261316 in the ALDH1A2 gene and uncontrolled blood pressure following treatment with a thiazide diuretic/β-blocker combination in white participants of the PEAR study [ 101 ]. The results of the INVEST study confirmed the aforementioned findings [ 101 ].…”

Section: Diureticsmentioning

confidence: 99%

“…A GWAS analysis found a relationship between the SNP rs261316 in the ALDH1A2 gene and uncontrolled blood pressure following treatment with a thiazide diuretic/β-blocker combination in white participants of the PEAR study [ 101 ]. The results of the INVEST study confirmed the aforementioned findings [ 101 ]. Other GWAS studies identified various additional loci associated with BP responses to HCTZ in different ethnic groups [ 16 , 102 , 103 ].…”

Section: Diureticsmentioning

confidence: 99%

Pharmacogenomics of Hypertension Treatment

Rysz

Franczyk

Rysz-Górzyńska

et al. 2020

IJMS

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Hypertension is one of the strongest modifiable cardiovascular risk factors, affecting an increasing number of people worldwide. Apart from poor medication adherence, the low efficacy of some therapies could also be related to inter-individual genetic variability. Genetic studies of families revealed that heritability accounts for 30% to 50% of inter-individual variation in blood pressure (BP). Genetic factors not only affect blood pressure (BP) elevation but also contribute to inter-individual variability in response to antihypertensive treatment. This article reviews the recent pharmacogenomics literature concerning the key classes of antihypertensive drugs currently in use (i.e., diuretics, β-blockers, ACE inhibitors, ARB, and CCB). Due to the numerous studies on this topic and the sometimes-contradictory results within them, the presented data are limited to several selected SNPs that alter drug response. Genetic polymorphisms can influence drug responses through genes engaged in the pathogenesis of hypertension that are able to modify the effects of drugs, modifications in drug–gene mechanistic interactions, polymorphisms within drug-metabolizing enzymes, genes related to drug transporters, and genes participating in complex cascades and metabolic reactions. The results of numerous studies confirm that genotype-based antihypertension therapies are the most effective and may help to avoid the occurrence of major adverse events, as well as decrease the costs of treatment. However, the genetic heritability of drug response phenotypes seems to remain hidden in multigenic and multifactorial complex traits. Therefore, further studies are required to analyze all associations and formulate final genome-based treatment recommendations.

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Genetic Variants Associated With Uncontrolled Blood Pressure on Thiazide Diuretic/β‐Blocker Combination Therapy in the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) and INVEST (International Verapamil‐SR Trandolapril Study) Trials

Cited by 19 publications

References 65 publications

<p>Pharmacogenomics And Hypertension: Current Insights</p>

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Genetic and Common Environmental Contributions to Familial Resemblances in Plasma Carotenoid Concentrations in Healthy Families

Pharmacogenomics of Hypertension Treatment

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