The Experts below are selected from a list of 3522 Experts worldwide ranked by ideXlab platform
Eric Boerwinkle - One of the best experts on this subject based on the ideXlab platform.
-
Pharmacogenetic Effect of the Stromelysin (MMP3) Polymorphism on Stroke Risk in Relation to Antihypertensive Treatment The Genetics of Hypertension Associated Treatment Study
2016Co-Authors: Eric Boerwinkle, Phd Donna, K. ArnettAbstract:Background and Purpose—Atherothrombotic diseases including stroke share a common etiology of atherosclerosis, and susceptibility to atherosclerosis has a genetic component. Stromelysin-1 (matrix metalloproteinase-3 [MMP3]) regulates arterial matrix composition and is a candidate gene for atherothrombosis. A common polymorphism of MMP3 alters expression levels and affects atherosclerotic progression and plaque stability. As part of the Genetics of Hypertension Associated Treatment study, ancillary to the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, we evaluated the 5A/6A polymorphism in MMP3 to determine its association with stroke and determine whether it modifies clinical outcome response to blood pressure–lowering drugs. Methods—The effect of the MMP3 5A/6A polymorphism on stroke rates was examined by using multivariate-adjusted Cox regression models, including a test for interactions between genotype and antihypertensive drug class. Results—Compared with participants treated with chlorthalidone with the 6A/6A genotype, individuals with the 6A/6A genotype randomized to lisinopril had higher stroke rates (hazard ratio1.32; 95 % CI, 1.08 to 1.61; P0.007) and 5A/6A individuals taking lisinopril had lower stroke rates (hazard ratiointeraction0.74; 95 % CI, 0.53 to 1.04; Pinteraction0.08), whereas 5A/5A individuals taking lisinopril had the lowest stroke rate (hazard ratiointeraction0.51; 95 % CI, 0.31 to 0.85; Pinteraction0.009). There were no pharmacogenetic differences in stroke rate by genotype in patients taking amlodipine or doxazosin vs chlorthalidone
-
The effects of genes implicated in cardiovascular disease on blood pressure response to treatment among treatment-naive hypertensive African Americans in the GenHAT study
Journal of Human Hypertension, 2016Co-Authors: A N Do, John H. Eckfeldt, Eric Boerwinkle, B R Davis, D K Arnett, C E Ford, A I Lynch, S A Claas, H K Tiwari, M R IrvinAbstract:African Americans have the highest prevalence of Hypertension in the United States. Blood pressure (BP) control is important to reduce cardiovascular disease-related morbidity and mortality in this ethnic group. Genetic variants have been found to be associated with BP response to treatment. Previous pharmacogenetic studies of BP response to treatment in African Americans suffer limitations of small sample size as well as a limited number of candidate genes, and often focused on one antihypertensive treatment. Using 1131 African-American treatment-naive participants from the Genetics of Hypertension Associated Treatment Study, we examined whether variants in 35 candidate genes might modulate BP response to four different antihypertensive medications, including an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), and an a-adrenergic blocker (doxazosin) as compared with a thiazide diuretic (chlorthalidone) after 6 months of follow-up. Several suggestive gene by treatment interactions were identified. For example, among participants with two minor alleles of renin rs6681776, diastolic BP response was much improved on doxazosin compared with chlorthalidone (on average −9.49 mm Hg vs −1.70 mm Hg) ( P =0.007). Although several suggestive loci were identified, none of the findings passed significance criteria after correction for multiple testing. Given the impact of Hypertension and its sequelae in this population, this research highlights the potential for genetic factors to contribute to BP response to treatment. Continued concerted research efforts focused on Genetics are needed to improve treatment response in this high-risk group.
-
pharmacogenetic effect of the stromelysin mmp3 polymorphism on stroke risk in relation to antihypertensive treatment the Genetics of Hypertension associated treatment study
Stroke, 2011Co-Authors: Richard Sherva, Charles E Ford, Barry R. Davis, John H. Eckfeldt, Eric Boerwinkle, Donna K ArnettAbstract:Background and Purpose—Atherothrombotic diseases including stroke share a common etiology of atherosclerosis, and susceptibility to atherosclerosis has a genetic component. Stromelysin-1 (matrix metalloproteinase-3 [MMP3]) regulates arterial matrix composition and is a candidate gene for atherothrombosis. A common polymorphism of MMP3 alters expression levels and affects atherosclerotic progression and plaque stability. As part of the Genetics of Hypertension Associated Treatment study, ancillary to the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, we evaluated the 5A/6A polymorphism in MMP3 to determine its association with stroke and determine whether it modifies clinical outcome response to blood pressure–lowering drugs. Methods—The effect of the MMP3 5A/6A polymorphism on stroke rates was examined by using multivariate-adjusted Cox regression models, including a test for interactions between genotype and antihypertensive drug class. Results—Compared with participants treated with ...
-
antihypertensive therapy the α adducin polymorphism and cardiovascular disease in high risk hypertensive persons the Genetics of Hypertension associated treatment study
Pharmacogenomics Journal, 2007Co-Authors: Barry R. Davis, C Leiendeckerfoster, Charles E Ford, Michael B Miller, Donna K Arnett, Henry R Black, Eric Boerwinkle, John H. EckfeldtAbstract:Antihypertensive therapy, the α -adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study
-
Antihypertensive therapy, the α-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study
The Pharmacogenomics Journal, 2007Co-Authors: B R Davis, Eric Boerwinkle, D K Arnett, C E Ford, C Leiendecker-foster, M B Miller, H Black, John H. EckfeldtAbstract:In a double-blind, outcome trial conducted in hypertensive patients randomized to chlorthalidone (C), amlodipine (A), lisinopril (L), or doxazosin (D), the α -adducin Gly460Trp polymorphism was typed ( n =36 913). Mean follow-up was 4.9 years. Relative risks (RRs) of chlorthalidone versus other treatments were compared between genotypes (Gly/Gly+Gly/Trp versus Trp/Trp). Primary outcome was coronary heart disease (CHD). Coronary heart disease incidence did not differ among treatments or genotypes nor was there any interaction between treatment and genotype ( P =0.660). Subgroup analyses indicated that Trp allele carriers had greater CHD risk with C versus A+L in women (RR=1.31) but not men (RR=0.91) with no RR gender differences for non-carriers (gender–gene–treatment interaction, P =0.002). The α -adducin gene is not an important modifier of antihypertensive treatment on cardiovascular risk, but women Trp allele carriers may have increased CHD risk if treated with C versus A or L. This must be confirmed to have implications for Hypertension treatment.
Donna K Arnett - One of the best experts on this subject based on the ideXlab platform.
-
Genetic and Adverse Health Outcome Associations with Treatment Resistant Hypertension in GenHAT.
International journal of hypertension, 2013Co-Authors: Amy I. Lynch, Charles E Ford, Barry R. Davis, John H. Eckfeldt, Marguerite R. Irvin, Donna K ArnettAbstract:Treatment resistant Hypertension (TRH) is defined as uncontrolled Hypertension (HTN) despite the use of ≥3 antihypertensive medication classes or controlled HTN while treated with ≥4 antihypertensive medication classes. Risk factors for TRH include increasing age, diminished kidney function, higher body mass index, diabetes, and African American (AA) race. Importantly, previous studies suggest a genetic role in TRH, although the Genetics of TRH are largely understudied. With 2203 treatment resistant cases and 2354 treatment responsive controls (36% AA) from the Genetics of Hypertension Associated Treatment Study (GenHAT), we assessed the association of 78 candidate gene polymorphisms with TRH status using logistic regression. After stratifying by race and adjusting for potential confounders, there were 2 genetic variants in the AGT gene (rs699, rs5051) statistically significantly associated with TRH among white participants. The Met allele of rs699 and the G allele of rs5051 were positively associated with TRH: (1.12–1.44), , and (1.20–1.53), , respectively. There was no similar association among AA participants (race interaction for rs699 and for rs5051). This research contributes to our understanding of the genetic basis of TRH, and further genetic studies of TRH may help reach the goal of better clinical outcomes for hypertensive patients.
-
pharmacogenetic effect of the stromelysin mmp3 polymorphism on stroke risk in relation to antihypertensive treatment the Genetics of Hypertension associated treatment study
Stroke, 2011Co-Authors: Richard Sherva, Charles E Ford, Barry R. Davis, John H. Eckfeldt, Eric Boerwinkle, Donna K ArnettAbstract:Background and Purpose—Atherothrombotic diseases including stroke share a common etiology of atherosclerosis, and susceptibility to atherosclerosis has a genetic component. Stromelysin-1 (matrix metalloproteinase-3 [MMP3]) regulates arterial matrix composition and is a candidate gene for atherothrombosis. A common polymorphism of MMP3 alters expression levels and affects atherosclerotic progression and plaque stability. As part of the Genetics of Hypertension Associated Treatment study, ancillary to the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, we evaluated the 5A/6A polymorphism in MMP3 to determine its association with stroke and determine whether it modifies clinical outcome response to blood pressure–lowering drugs. Methods—The effect of the MMP3 5A/6A polymorphism on stroke rates was examined by using multivariate-adjusted Cox regression models, including a test for interactions between genotype and antihypertensive drug class. Results—Compared with participants treated with ...
-
Genetics of Hypertension and Cardiovascular Disease and Their Interconnected Pathways: Lessons from Large Studies
Current Hypertension Reports, 2011Co-Authors: Aldi T. Kraja, Donna K Arnett, Steven C. Hunt, Victor G. Dávila-román, Michael A. ProvinceAbstract:Blood pressure (BP), Hypertension (HT) and cardiovascular disease (CVD) are common complex phenotypes, which are affected by multiple genetic and environmental factors. This article describes recent genome-wide association studies (GWAS) that have reported causative variants for BP/HT and CVD/heart traits and analyzes the overlapping associated gene polymorphisms. It also examines potential replication of findings from the HyperGEN data on African Americans and whites. Several genes involved in BP/HT regulation also appear to be involved in CVD. A better picture is emerging, with overlapping hot-spot regions and with interconnected pathways between BP/HT and CVD. A systemic approach to full understanding of BP/HT and CVD development and their progression to disease may lead to the identification of gene targets and pathways for the development of novel therapeutic interventions.
-
Genetics of Hypertension and Cardiovascular Disease and Their Interconnected Pathways: Lessons from Large Studies
Current Hypertension Reports, 2011Co-Authors: Aldi T. Kraja, Donna K Arnett, Steven C. Hunt, Victor G. Dávila-román, D. C. Rao, Michael A. ProvinceAbstract:Blood pressure (BP), Hypertension (HT) and cardiovascular disease (CVD) are common complex phenotypes, which are affected by multiple genetic and environmental factors. This article describes recent genome-wide association studies (GWAS) that have reported causative variants for BP/HT and CVD/heart traits and analyzes the overlapping associated gene polymorphisms. It also examines potential replication of findings from the HyperGEN data on African Americans and whites. Several genes involved in BP/HT regulation also appear to be involved in CVD. A better picture is emerging, with overlapping hot-spot regions and with interconnected pathways between BP/HT and CVD. A systemic approach to full understanding of BP/HT and CVD development and their progression to disease may lead to the identification of gene targets and pathways for the development of novel therapeutic interventions.
-
antihypertensive therapy the α adducin polymorphism and cardiovascular disease in high risk hypertensive persons the Genetics of Hypertension associated treatment study
Pharmacogenomics Journal, 2007Co-Authors: Barry R. Davis, C Leiendeckerfoster, Charles E Ford, Michael B Miller, Donna K Arnett, Henry R Black, Eric Boerwinkle, John H. EckfeldtAbstract:Antihypertensive therapy, the α -adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study
John H. Eckfeldt - One of the best experts on this subject based on the ideXlab platform.
-
The effects of genes implicated in cardiovascular disease on blood pressure response to treatment among treatment-naive hypertensive African Americans in the GenHAT study
Journal of Human Hypertension, 2016Co-Authors: A N Do, John H. Eckfeldt, Eric Boerwinkle, B R Davis, D K Arnett, C E Ford, A I Lynch, S A Claas, H K Tiwari, M R IrvinAbstract:African Americans have the highest prevalence of Hypertension in the United States. Blood pressure (BP) control is important to reduce cardiovascular disease-related morbidity and mortality in this ethnic group. Genetic variants have been found to be associated with BP response to treatment. Previous pharmacogenetic studies of BP response to treatment in African Americans suffer limitations of small sample size as well as a limited number of candidate genes, and often focused on one antihypertensive treatment. Using 1131 African-American treatment-naive participants from the Genetics of Hypertension Associated Treatment Study, we examined whether variants in 35 candidate genes might modulate BP response to four different antihypertensive medications, including an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), and an a-adrenergic blocker (doxazosin) as compared with a thiazide diuretic (chlorthalidone) after 6 months of follow-up. Several suggestive gene by treatment interactions were identified. For example, among participants with two minor alleles of renin rs6681776, diastolic BP response was much improved on doxazosin compared with chlorthalidone (on average −9.49 mm Hg vs −1.70 mm Hg) ( P =0.007). Although several suggestive loci were identified, none of the findings passed significance criteria after correction for multiple testing. Given the impact of Hypertension and its sequelae in this population, this research highlights the potential for genetic factors to contribute to BP response to treatment. Continued concerted research efforts focused on Genetics are needed to improve treatment response in this high-risk group.
-
Genetic and Adverse Health Outcome Associations with Treatment Resistant Hypertension in GenHAT.
International journal of hypertension, 2013Co-Authors: Amy I. Lynch, Charles E Ford, Barry R. Davis, John H. Eckfeldt, Marguerite R. Irvin, Donna K ArnettAbstract:Treatment resistant Hypertension (TRH) is defined as uncontrolled Hypertension (HTN) despite the use of ≥3 antihypertensive medication classes or controlled HTN while treated with ≥4 antihypertensive medication classes. Risk factors for TRH include increasing age, diminished kidney function, higher body mass index, diabetes, and African American (AA) race. Importantly, previous studies suggest a genetic role in TRH, although the Genetics of TRH are largely understudied. With 2203 treatment resistant cases and 2354 treatment responsive controls (36% AA) from the Genetics of Hypertension Associated Treatment Study (GenHAT), we assessed the association of 78 candidate gene polymorphisms with TRH status using logistic regression. After stratifying by race and adjusting for potential confounders, there were 2 genetic variants in the AGT gene (rs699, rs5051) statistically significantly associated with TRH among white participants. The Met allele of rs699 and the G allele of rs5051 were positively associated with TRH: (1.12–1.44), , and (1.20–1.53), , respectively. There was no similar association among AA participants (race interaction for rs699 and for rs5051). This research contributes to our understanding of the genetic basis of TRH, and further genetic studies of TRH may help reach the goal of better clinical outcomes for hypertensive patients.
-
pharmacogenetic effect of the stromelysin mmp3 polymorphism on stroke risk in relation to antihypertensive treatment the Genetics of Hypertension associated treatment study
Stroke, 2011Co-Authors: Richard Sherva, Charles E Ford, Barry R. Davis, John H. Eckfeldt, Eric Boerwinkle, Donna K ArnettAbstract:Background and Purpose—Atherothrombotic diseases including stroke share a common etiology of atherosclerosis, and susceptibility to atherosclerosis has a genetic component. Stromelysin-1 (matrix metalloproteinase-3 [MMP3]) regulates arterial matrix composition and is a candidate gene for atherothrombosis. A common polymorphism of MMP3 alters expression levels and affects atherosclerotic progression and plaque stability. As part of the Genetics of Hypertension Associated Treatment study, ancillary to the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, we evaluated the 5A/6A polymorphism in MMP3 to determine its association with stroke and determine whether it modifies clinical outcome response to blood pressure–lowering drugs. Methods—The effect of the MMP3 5A/6A polymorphism on stroke rates was examined by using multivariate-adjusted Cox regression models, including a test for interactions between genotype and antihypertensive drug class. Results—Compared with participants treated with ...
-
antihypertensive therapy the α adducin polymorphism and cardiovascular disease in high risk hypertensive persons the Genetics of Hypertension associated treatment study
Pharmacogenomics Journal, 2007Co-Authors: Barry R. Davis, C Leiendeckerfoster, Charles E Ford, Michael B Miller, Donna K Arnett, Henry R Black, Eric Boerwinkle, John H. EckfeldtAbstract:Antihypertensive therapy, the α -adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study
-
Antihypertensive therapy, the α-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study
The Pharmacogenomics Journal, 2007Co-Authors: B R Davis, Eric Boerwinkle, D K Arnett, C E Ford, C Leiendecker-foster, M B Miller, H Black, John H. EckfeldtAbstract:In a double-blind, outcome trial conducted in hypertensive patients randomized to chlorthalidone (C), amlodipine (A), lisinopril (L), or doxazosin (D), the α -adducin Gly460Trp polymorphism was typed ( n =36 913). Mean follow-up was 4.9 years. Relative risks (RRs) of chlorthalidone versus other treatments were compared between genotypes (Gly/Gly+Gly/Trp versus Trp/Trp). Primary outcome was coronary heart disease (CHD). Coronary heart disease incidence did not differ among treatments or genotypes nor was there any interaction between treatment and genotype ( P =0.660). Subgroup analyses indicated that Trp allele carriers had greater CHD risk with C versus A+L in women (RR=1.31) but not men (RR=0.91) with no RR gender differences for non-carriers (gender–gene–treatment interaction, P =0.002). The α -adducin gene is not an important modifier of antihypertensive treatment on cardiovascular risk, but women Trp allele carriers may have increased CHD risk if treated with C versus A or L. This must be confirmed to have implications for Hypertension treatment.
Anna F. Dominiczak - One of the best experts on this subject based on the ideXlab platform.
-
Genetics of Hypertension and Heart Failure
Updates in Hypertension and Cardiovascular Protection, 2019Co-Authors: Sandosh Padmanabhan, Alisha Aman, Anna F. DominiczakAbstract:Hypertension and heart failure are leading causes of death and disability worldwide. Both are complex multifactorial conditions with Hypertension and heart failure at either ends of the cardiovascular continuum. Rare mutations resulting in monogenic forms of Hypertension, hypotension and cardiomyopathies highlight the importance of Genetics in disease causation and consequent implications for disease prediction and treatment. Advances in genomics have accelerated over the last decade leading to an unparalleled leap in our understanding of the genetic architecture of both Hypertension and heart failure. In this chapter, we describe the current state of the art in the Genetics of both conditions, Hypertension and heart failure, focussing on biologic pathways that are perturbed and opportunities for early detection and treatment.
-
Genetics of Hypertension: From experimental animals to humans
Biochimica et Biophysica Acta - Molecular Basis of Disease, 2010Co-Authors: Christian Delles, Sandosh Padmanabhan, Martin W. Mcbride, Delyth Graham, Anna F. DominiczakAbstract:Essential Hypertension affects 20 to 30 % of the population worldwide and contributes significantly to cardiovascular mortality and morbidity. Heridability of blood pressure is around 15 to 40 % but there are also substantial environmental factors affecting blood pressure variability. 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. Animal models of Hypertension, particularly in the rat, have led to the discovery of quantitative trait loci harbouring one or several Hypertension related genes, but translation of these findings into human essential Hypertension remains challenging. 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.
-
Genetics of Hypertension
2007Co-Authors: Anna F. Dominiczak, John M. C. ConnellAbstract:Overview and introduction. Genetic epidemiology of Hypertension and its complications. Meta-analyses in Genetics: examples from the renin-angiotensin system. Gene-gene and gene-environment interactions in normotensive and hypertensive populations. Genetic studies of inherited Hypertension in the rat. Genetic studies of inherited Hypertension in the mouse. Transgenic rats and Hypertension. Gene targeting in mice to study blood pressure regulation. Monogenic syndromes leading to Hypertension and hypotension. Candidate genes within the renin-angiotensin system in essential Hypertension. Genetics of pre-eclamsia. Genetics of stroke. Adducin gene as a paradigm for functional studies. Genome scans in Hypertension. Comparative genome analysis. Attaching physiology to the genome. PharmacoGenetics and pharmacogenomics in cardiovascular medicine. Gene therapy for Hypertension: fact or fiction?.
-
haplotypes of the wnk1 gene associate with blood pressure variation in a severely hypertensive population from the british Genetics of Hypertension study
Human Molecular Genetics, 2005Co-Authors: Stephen Newhouse, J Pembroke, Charles A Mein, Chris Wallace, Martin Farrall, Morris J Brown, Richard Dobson, David F. Clayton, Nilesh J. Samani, Anna F. DominiczakAbstract:Mutations in the WNK1 gene cause Gordon’s syndrome, a rare Mendelian form of Hypertension. We assessed whether common WNK1 variants might also contribute to essential Hypertension (EH), a multifactorial disorder affecting >25% of the adult population worldwide. A panel of 19 single nucleotide polymorphisms (SNPs) spanning the gene was selected from public databases and was genotyped in 100 white European families to determine the pattern of linkage disequilibrium, haplotype structure and tagging SNPs for the WNK1 locus. Eight tagging SNPs were identified with 90% power to predict common WNK1 haplotypes and SNPs. Family-based association tests were used to test for association with EH and severity of Hypertension in 712 severely hypertensive families from the MRC British Genetics of Hypertension study resource. No association was found between WNK1 polymorphisms or haplotypes with Hypertension; however, one SNP rs1468326, located 3 kb from the WNK1 promoter, was found to be nominally associated with severity of Hypertension, with both systolic blood pressure (BP) (Z 51 2.24, P 5 0.025) and diastolic BP (Z 51 1.99, P 5 0.046). We also found nominal support for association of one common WNK1 haplotype with increased systolic BP (Z 51 1.91, P 5 0.053). This is the first study to perform haplotype association analysis of the WNK1 gene with EH. This finding of association between a SNP near the promoter region and the severity of Hypertension suggests that increased expression of WNK1 might contribute to BP variability and susceptibility to EH similar to the mechanism of Hypertension observed in Gordon’s syndrome.
-
haplotypes of the wnk1 gene associate with blood pressure variation in a severely hypertensive population from the british Genetics of Hypertension study
Human Molecular Genetics, 2005Co-Authors: Stephen Newhouse, J Pembroke, Charles A Mein, Chris Wallace, Martin Farrall, Morris J Brown, Richard Dobson, David F. Clayton, Nilesh J. Samani, Anna F. DominiczakAbstract:Mutations in the WNK1 gene cause Gordon’s syndrome, a rare Mendelian form of Hypertension. We assessed whether common WNK1 variants might also contribute to essential Hypertension (EH), a multifactorial disorder affecting >25% of the adult population worldwide. A panel of 19 single nucleotide polymorphisms (SNPs) spanning the gene was selected from public databases and was genotyped in 100 white European families to determine the pattern of linkage disequilibrium, haplotype structure and tagging SNPs for the WNK1 locus. Eight tagging SNPs were identified with 90% power to predict common WNK1 haplotypes and SNPs. Family-based association tests were used to test for association with EH and severity of Hypertension in 712 severely hypertensive families from the MRC British Genetics of Hypertension study resource. No association was found between WNK1 polymorphisms or haplotypes with Hypertension; however, one SNP rs1468326, located 3 kb from the WNK1 promoter, was found to be nominally associated with severity of Hypertension, with both systolic blood pressure (BP) (Z 51 2.24, P 5 0.025) and diastolic BP (Z 51 1.99, P 5 0.046). We also found nominal support for association of one common WNK1 haplotype with increased systolic BP (Z 51 1.91, P 5 0.053). This is the first study to perform haplotype association analysis of the WNK1 gene with EH. This finding of association between a SNP near the promoter region and the severity of Hypertension suggests that increased expression of WNK1 might contribute to BP variability and susceptibility to EH similar to the mechanism of Hypertension observed in Gordon’s syndrome.
Barry R. Davis - One of the best experts on this subject based on the ideXlab platform.
-
Genetic and Adverse Health Outcome Associations with Treatment Resistant Hypertension in GenHAT.
International journal of hypertension, 2013Co-Authors: Amy I. Lynch, Charles E Ford, Barry R. Davis, John H. Eckfeldt, Marguerite R. Irvin, Donna K ArnettAbstract:Treatment resistant Hypertension (TRH) is defined as uncontrolled Hypertension (HTN) despite the use of ≥3 antihypertensive medication classes or controlled HTN while treated with ≥4 antihypertensive medication classes. Risk factors for TRH include increasing age, diminished kidney function, higher body mass index, diabetes, and African American (AA) race. Importantly, previous studies suggest a genetic role in TRH, although the Genetics of TRH are largely understudied. With 2203 treatment resistant cases and 2354 treatment responsive controls (36% AA) from the Genetics of Hypertension Associated Treatment Study (GenHAT), we assessed the association of 78 candidate gene polymorphisms with TRH status using logistic regression. After stratifying by race and adjusting for potential confounders, there were 2 genetic variants in the AGT gene (rs699, rs5051) statistically significantly associated with TRH among white participants. The Met allele of rs699 and the G allele of rs5051 were positively associated with TRH: (1.12–1.44), , and (1.20–1.53), , respectively. There was no similar association among AA participants (race interaction for rs699 and for rs5051). This research contributes to our understanding of the genetic basis of TRH, and further genetic studies of TRH may help reach the goal of better clinical outcomes for hypertensive patients.
-
pharmacogenetic effect of the stromelysin mmp3 polymorphism on stroke risk in relation to antihypertensive treatment the Genetics of Hypertension associated treatment study
Stroke, 2011Co-Authors: Richard Sherva, Charles E Ford, Barry R. Davis, John H. Eckfeldt, Eric Boerwinkle, Donna K ArnettAbstract:Background and Purpose—Atherothrombotic diseases including stroke share a common etiology of atherosclerosis, and susceptibility to atherosclerosis has a genetic component. Stromelysin-1 (matrix metalloproteinase-3 [MMP3]) regulates arterial matrix composition and is a candidate gene for atherothrombosis. A common polymorphism of MMP3 alters expression levels and affects atherosclerotic progression and plaque stability. As part of the Genetics of Hypertension Associated Treatment study, ancillary to the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, we evaluated the 5A/6A polymorphism in MMP3 to determine its association with stroke and determine whether it modifies clinical outcome response to blood pressure–lowering drugs. Methods—The effect of the MMP3 5A/6A polymorphism on stroke rates was examined by using multivariate-adjusted Cox regression models, including a test for interactions between genotype and antihypertensive drug class. Results—Compared with participants treated with ...
-
antihypertensive therapy the α adducin polymorphism and cardiovascular disease in high risk hypertensive persons the Genetics of Hypertension associated treatment study
Pharmacogenomics Journal, 2007Co-Authors: Barry R. Davis, C Leiendeckerfoster, Charles E Ford, Michael B Miller, Donna K Arnett, Henry R Black, Eric Boerwinkle, John H. EckfeldtAbstract:Antihypertensive therapy, the α -adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study
-
absence of an interaction between the angiotensin converting enzyme insertion deletion polymorphism and pravastatin on cardiovascular disease in high risk hypertensive patients the Genetics of Hypertension associated treatment genhat study
American Heart Journal, 2007Co-Authors: C Leiendeckerfoster, Charles E Ford, Barry R. Davis, Michael B Miller, Donna K Arnett, Eric Boerwinkle, Anke Hilse Maitlandvan Der Zee, O H Klungel, John H. EckfeldtAbstract:Background The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) insertion-deletion (ID) polymorphism interacts with pravastatin to modify the risk of coronary heart disease (CHD) and other cardiovascular end points in a large clinical trial. Methods GenHAT is an ancillary study of the ALLHAT. The ACE ID genotyped population in the lipid-lowering arm of ALLHAT included 9467 participants randomly assigned to pravastatin (n = 4741) or to usual care (n = 4726). The efficacy of pravastatin in reducing the risk of primary outcome (all-cause mortality) and secondary outcomes (fatal CHD and nonfatal myocardial infarction, cardiovascular disease [CVD] mortality, CHD, stroke, other CVD, non-CVD mortality, stroke, and heart failure) was compared between the genotype strata (dominant model ID + II vs DD, additive model II vs ID vs DD), by examining an interaction term in a Cox proportional hazards model. Results The relative risk of fatal CHD and nonfatal myocardial infarction among subjects randomized to pravastatin compared with subjects randomized to usual care was similar in subjects with the II genotype (hazard ratio [HR] 0.84, 95% CI 0.59-1.18), the ID genotype (HR 0.84, 95% CI 0.68-1.03), and the DD genotype (HR 0.99, 95% CI 0.77-1.27). Conclusions We found no evidence that the ACE ID genotype was a major modifier of the efficacy of pravastatin in reducing the risk of cardiovascular events.
-
pharmacogenetic association of the angiotensin converting enzyme insertion deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment the Genetics of Hypertension associated treatment genhat study
Circulation, 2005Co-Authors: Donna K Arnett, C Leiendeckerfoster, Charles E Ford, Barry R. Davis, Michael B Miller, Henry R Black, Eric Boerwinkle, John H. EckfeldtAbstract:Background— Previous studies have reported that blood pressure response to antihypertensive medications is influenced by genetic variation in the renin-angiotensin-aldosterone system, but no clinical trails have tested whether the ACE insertion/deletion (I/D) polymorphism modifies the association between the type of medication and multiple cardiovascular and renal phenotypes. Methods and Results— We used a double-blind, active-controlled randomized trial of antihypertensive treatment that included hypertensives ≥55 years of age with ≥1 risk factor for cardiovascular disease. ACE I/D genotypes were determined in 37 939 participants randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatments and followed up for 4 to 8 years. Primary outcomes included fatal coronary heart disease (CHD) and/or nonfatal myocardial infarction. Secondary outcomes included stroke, all-cause mortality, combined CHD, and combined cardiovascular disease. Fatal and nonfatal CHD occurred in 3096 individuals during fo...