DNArterial®

Study of molecular markers of essential hypertension
and associated cardiovascular events

With: Pharmacogenetics Report and Disease Risk Score

 

NEW

With Disease Risk Score Evaluation

Learn more

Did you know that:

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40% of adults aged 25 and over have Arterial Hypertension

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Heritability estimated to vary between 35% and 50% in the majority of studies

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57% of hypertensive patients have non-controlled  hypertension due to poor treatment compliance or inadequate treatment

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AHTN is the leading cause of mortality, responsible for 13% of deaths globally (WHO).

According to the World Heart Federation, Hypertension is a risk factor for coronary heart disease and the single most important risk factor for stroke. It causes about 50% of ischaemic strokes and increases the risk of hemorrhagic stroke.

Why is high blood pressure a problem?


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Arterial Hypertension is the major cause of cardiovascular diseases (CVD), which are the leading cause of death worldwide.

High blood pressure is a major risk factor for CVD such as stroke, myocardial infarction, coronary heart disease, peripheral arterial disease, renovascular disease, arterial aneurysms and heart failure.

AHTN is a disease that often goes undetected



DNArterial® Genetic Test

Study of molecular markers of essential hypertension and associated cardiovascular events

A genetic test focused on prevention and control of AHTN early in life.


How is DNArterial®  genetic test helpful? 
  • Evaluates the risk for Essential Hypertension in individuals with pre-hypertension values and moderate risk
  • Informs about the effectiveness of anti-hypertensive therapies according to genetic makeup (pharmacogenetics).
  • Includes guidelines and recommendations from  Eighth Joint National Committee (JNC8)
  • Evaluate the predisposition for Essential Hypertension early in life.
  • Confirm the genetic cause and support the clinical diagnosis of Essential Hypertension.

 

  • Assess how the disease may develop trough age.

 

  • Inform about the effectiveness of anti-hypertensive therapies (drug prescription).

 

Precision medicine through molecular diagnostics


DNArterial® is suitable to:

– individuals at risk (genetic and environmental) for developing AHTN;

– individuals with a family history of AHTN;

– individuals with clinical diagnosis of AHTN;

– individuals with severe forms of AHTN;

– individuals with resistant AHTN; – individuals submitted to renal-denervation;

– individuals with cardiovascular diseases;

– women with an history of preeclampsia or gestational hypertension

DNArterialPLUS®

A more complete genetic test for AHTN

DNArterial short vs plus


DNArterialPLUS® is particular useful in the following cases:

1. Mendelian diseases associated with hypertension

2. Individuals with resistant arterial hypertension.

3. Individuals submitted to renal-denervation.

DNArterial® Benefits

WITHOUT DISEASE SYMPTOMS

 

1. Preventive. Assess the risk of developing AHTN earlier in life allowing timely and preventive actions.

2. Simple. Only a blood or saliva sample is needed.

3. Unique. DNArterial® is a unique test in the market that accurately assesses the genetic risk for AHTN.

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WITH DISEASE SYMPTOMS

 1. Protective. Supports a more complete clinical evaluation concerning the causes, severity and progression of AHTN.

2. Complements. Complements clinical and biochemical diagnostic tests, thus avoiding disease aggravation.

3. Tailored therapeutics. Informs your doctor which drugs works best for the patient and which ones do not.

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DNArterial® only requires a blood sample 

It’s easy, fast and, most importantly, informative for medical diagnosis.

DNArterial® Testimonials

Personalized medicine will have a growing role and importance in the healthcare and Arterial Hypertension.

Drª. Maria Isabel Mendonça, Cardiologist, Department of Cardiology, Hospital Dr. Nelio Mendonça, Madeira, Portugal.


I congratulate HeartGenetics for the development of a test that enables the simultaneous evaluation of several metabolic axis associated with arterial hypertension.

Dr. Roberto Palma dos Reis, Associate Professor of Medicine (Cardiology), Faculty of Medical Sciences, Universidade Nova de Lisboa, Portugal


This genetic test should be seen as a tool for the correct decision making about diagnosis, non-pharmacological and personalized drug therapies of the sodium sensitivity in Arterial Hypertension and related situations.

Prof. Manuel Bicho, Professor at Faculty of Medicine, University of Lisbon, Portugal

DNArterial® vs DNArterial PLUS®

 

DNArterial® DNArterial PLUS®
Genetic Variants 51  112 (full panel)
Support clinical evaluation icon-small-check  icon-small-check
Identification of genetic cause of AHTN  icon-small-check  icon-small-check
Suitable for Screening  icon-small-check  icon-small-check
Genetic alterations for HIGH risk of AHTN  icon-small-check  icon-small-check
Genetic alterations for LOW risk of AHTN  icon-small-check

 ADDITIONAL INFORMATION

DNArterial® Gene Panel

ACE2(2), ADD1(1), ADRA1A(1), ADRB1(2), ADRB2(3), AGT(4), AGTR1(2), AGTR2(2), CACNA1C(1), CACNA1H(1), CACNB2(1) CALCA(1), CLCNKA(1), CLCNKB(1), CYP4A11(1), ECE1(2), EDN1(1), EDN2(1), EDNRA(1), FGF5(1), GNB3(1), GRK4(3), HSD11B2(1), NEDD4L(1), NOS2(1), NOS3(1), NPPA(2), NR3C2(1), REN(4), SCNN1A(1), SCNN1B(1), SLC12A3(1), STK39(1), WNK1(2)

DNArterial PLUS® Gene Panel

ACE (3), ACE2(2), ADC(1), ADD1(1), ADRA1A(2), ADRA2B(1), ADRB1(2), ADRB2(3), AGT(9), AGTR1(2), AGTR2(2), BDKRB2(1), CACNA1C(1), CACNA1H(1), CACNB2(1), CALCA(1), CLCNKA(1), CLCNKB(1), CORIN(2), CYBA(2), CYP11B1(3), CYP11B2(1), CYP17A1(1), CYP2J2(1), CYP4A11(1), DRD3(1), ECE1(2), EDN1(2), EDN2(1), EDNRA(1), FGF5(1), GCH1(1), GNB3(1), GRK4(3), HSD11B2(3), KCNJ1(4), KCNJ5(1), KCNMA1(1), KCNMB1(2), NEDD4L(1), NOS2(1), NOS3(2), NPPA(3), NPPC(1), NPR1(1), NR3C2(3), REN(4), RETN(1), SCNN1A(2), SCNN1B(5), SCNN1G(3), SLC12A1(8), SLC12A3(2), STK39(1), VHL(2), WNK1(2)

Start improving AHTN diagnosis today

(Only for registered medical doctors, register here)

Download DNArterial® Requisition Form: PT | EN

Download DNArterialPLUS® Requisition Form: PT | EN


Go back to products  |  Download Product Sheet  |  Need further information? Contact us


DNArterial® Genetic Tests

The scientific background

 


1. Genetics of Arterial Hypertension

Genomic data obtained from Genome Wide Association (GWA) studies have contributed to the understanding of the genetic basis of hypertension.

In the case of AHTN, its applied the genotype-phenotype association model: “common disease, common variant”. In this model, common pathologies are due to allelic variants with a frequency higher than 5% in the overall population. (Nat Rev Genet 2008;9 (5):356-369).

DNArterial® is a genetic testing panel constituted by 51 genetic variants in 34 genes, which are considered to be genetic risk markers associated with arterial hypertension.

 


The proposed genetic panel evaluates the genetic alterations related to the regulation and/or dysfunction of:

 – the renin-angiotensin-aldosterone system (RAAS)

 – the vascular endothelium dysfunction

 – the renal-tubule

 – regulation of sodium channels

 – the autonomous  nervous system

 – the signal transduction system

 – mendelian diseases associated with hypertension

  DNArterial® – Study of molecular risk markers of high risk and prevalence for AHTN

34 Genes (51 Genetic variants)

ACE2(2), ADD1(1), ADRA1A(1), ADRB1(2), ADRB2(3), AGT(4), AGTR1(2), AGTR2(2), CACNA1C(1), CACNA1H(1), CACNB2(1) CALCA(1), CLCNKA(1), CLCNKB(1), CYP4A11(1), ECE1(2), EDN1(1), EDN2(1), EDNRA(1), FGF5(1), GNB3(1), GRK4(3), HSD11B2(1), NEDD4L(1), NOS2(1), NOS3(1), NPPA(2), NR3C2(1), REN(4), SCNN1A(1), SCNN1B(1), SLC12A3(1), STK39(1), WNK1(2)

DNArterial Plus ® – Study of molecular risk markers for AHTN

56 Genes (112 Genetic variants)

ACE (3), ACE2(2), ADC(1), ADD1(1), ADRA1A(2), ADRA2B(1), ADRB1(2), ADRB2(3), AGT(9), AGTR1(2), AGTR2(2), BDKRB2(1), CACNA1C(1), CACNA1H(1), CACNB2(1), CALCA(1), CLCNKA(1), CLCNKB(1), CORIN(2), CYBA(2), CYP11B1(3), CYP11B2(1), CYP17A1(1), CYP2J2(1), CYP4A11(1), DRD3(1), ECE1(2), EDN1(2), EDN2(1), EDNRA(1), FGF5(1), GCH1(1), GNB3(1), GRK4(3), HSD11B2(3), KCNJ1(4), KCNJ5(1), KCNMA1(1), KCNMB1(2), NEDD4L(1), NOS2(1), NOS3(2), NPPA(3), NPPC(1), NPR1(1), NR3C2(3), REN(4), RETN(1), SCNN1A(2), SCNN1B(5), SCNN1G(3), SLC12A1(8), SLC12A3(2), STK39(1), VHL(2), WNK1(2)


KEY GENES

ACE – Gene encoding for angiotensin-converting enzyme

The angiotensin-converting enzyme I (ACE) from the RAAS system encoded by the gene ACE, catalyses the conversion of the angiotensin I to angiotensin II (vasoconstrictor), the bradykinin degradation (vasodilator), has a crucial role on the sodium homeostasis and blood pressure control. The polymorphism insertion (I)/deletion (D) has been studied in patients with hypertension and its role has been assessed concerning the therapeutics effectiveness of the IECA and diuretics in several ethnic groups and in arterial hypertension associated diseases. .

The ACE concentration is interrelated with the genotype expression, being the D allele of related gene associated with elevated ACE levels in plasma. There are favourable results showing that hypertensive patients having the I / D polymorphism have increased efficacy in lowering blood pressure in response to diuretics – thiazides (Clin Sci (Lond). 2003 Nov;105(5):637-44.; Hypertens Res. 2003 Nov;26(11):881-6; Circulation. 2007 Feb 13;115(6):725-32; Chin Med J (Engl). 2007 May 5;120(9):782-6; Pharmacogenet Genomics. 2010 Feb;20(2):77-85).

Recently, Chung e co-workers (PLoS One. 2013;8(3):e56119) studied 305 young hypertensive individuals, from 1.168 patients, and identified a SNP associated with ACE activity, which, simultaneously, responded to IECA drug for regulating arterial blood pressure.

AGT – Gene encoding for angiotensinogen

The angiotensinogen (AGT) is a protein encoded by the AGT gene, which is cleaved by angiotensin-converting enzyme to generate the active enzyme angiotensin II in the liver and in α2-globulin fraction in plasma. In the RAAS system, the AGT protein is cleaved by renin and it is involved in the regulation of BP. The T235 and M235 polymorphisms on the associated gene are related to the susceptibility for hypertension and preeclampsia (Nature Genetics 1993; 4, 59-61).

The genetic variant M235T in African-Americans, which have a high prevalence for hypertension, has a frequency of 70% T235 homozygotes (HMZ), 28% T235 heterozygotes  (HTZ) and only 2% for M235 HMZ. In Caucasians the equivalent values were 12% HMZ and 46% HTZ for T235 allelic variant and 42% for M235.

AGT levels in African-Americans is on average 19% higher than that of Caucasians and it is interrelated with the frequency of the T235 allele – 81% in the African-American versus 42% in Caucasians, contributing to the hypertension susceptibility and increased risk of progression to CVD in African-Americans population (J Clin Invest. 1995 Mar;95 (3):948-53).

ADD1 – Gene encoding for alpha-adducin

The ADD-1 gene encodes one adducin alpha subunit (ADD-1). The ADD-1 is a cytoskeleton protein that modulates the surface expression of multiple transporters and ion pumps, and regulates the signal transduction that contributes to the sodium reabsorption and retention in the renal tubule and, subsequently, it is related to a greater susceptibility for hypertension.

The genetic variant Gly460Trp has been shown to be responsible for an increase Na-K pump activity and has been linked to salt-sensitivity in patients with essential hypertension (Lancet. 1997 May 10;349(9062):1353-7; Hypertension. 1999;34:1281–1286).

In a study performed in 2009, Italian patients heterozygous carriers of this variant showed a greater response to the therapy with hydrochlorothiazide in decreasing arterial blood pressure than those homozygous Gly/Gly patients. This association was not observed in subjects in the Finnish population (Am J Hypertens 2009 Feb;22 (2):169-75).

ADRB1 – Gene encoding for the B1-adrenergic receptor

ADRB1 gene encoding for the B1 adrenergic receptor is the target of the blocking β-adrenergic receptors drugs.

The Arg389Gly and Ser49Gly polymorphisms has been associated with antihypertensive drugs. For the Arg389 polymorfism it is detected an increased activity of the β1-adrenergic receptor and so it is expected that individuals with this variant have a better response to β-blocker therapy, particularly with metaprolol (Acta Pharmacol Sin. 2006 Feb;27(2):254-8; Pharmacogenomics J. 2008 Dec; 8(6):408-15). The allelic frequency of Arg389 polymorfism is 53% and 34% in Caucasians and African-Americans, respectively (Ann Med. 2012 Jun; 44 Suppl 1:S17-22). The Arg389Gly polymorphism was been associated with atenolol response in a study of 5,979 patients in the United States and Puerto Rico (Clin Pharmacol Ther. 2008 Dec;84(6):715-21)


2. What do  you get with a DNArterial® report?

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1. Integration.We analyse specific molecular markers known to date to be associated with arterial hypertension.

2. Pharmacogenetics. DNArterial® reports includes antihypertensive therapy according to  the identified ATHN genetic variants.

3. Supporting texts. Our reports include simple texts explaining the most relevant information.

4. Focus. Our methodology directly examines the presence or absence of a specific genetic alteration causing the disease.

5. Rigorous. DNArterial® tests have 99% accuracy. All evidence is supported based on scientific bibliography and validated by medical experts.


All DNArterial® reports have supporting texts for each genetic variant 

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Supporting text for each genetic variant includes, when available:

 – gene function in blood pressure homeostasis:

 – the association of the genetic variant with the clinical profile;

 – the prevalence of the genetic variant;

 – pharmacogenetics, if available for the genetic variant



DNArterial®  Pharmacogenetics


Tailored therapeutics


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The problem:

Despite multidrug therapy, blood pressure is frequently suboptimally controlled. Also, adverse drug effects often interfere with patients’ lifestyles and affect compliance.

The Solution:

PHARMACOGENETICS. The goal of pharmacogenetics in AHTN control is to associate the most appropriate therapeutics to each individual according to the identified genetic variant.


DNArterial® increases therapeutic efficacy and minimize adverse side effects, increasing patient compliance.

This personalised approach allows a better control of disease progression to a resistant form of hypertension, thus contributing to change the impact of arterial hypertension on morbidity and mortality.

The knowledge about the consequences of AHTN, both the environmental and the genetic risk factors associated with this pathology, is the first step for the control of hypertension and for the prevention of associated cardiovascular diseases.

3. What are the clinical guidelines for AHTN testing?


According to European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Guidelines for the management of arterial hypertension (2013):

” A family history of premature hypertension and/or premature CVD is an important first indicator of familial (genetic) predisposition to hypertension and CVD and may trigger clinically indicated genetic tests.”

“A positive family history is a frequent feature in hypertensive patients, with the heritability estimated to vary between 35% and 50% in the majority of studies and heritability has been confirmed for ambulatory BP”


According to Reappraisal of European guidelines on hypertension management: A European Society of Hypertension, Task Force document, 2011:

“Although it is possible that the use of two drugs together implies the administration of a futile one, searching for the most effective monotherapy in every given patient is painstaking, and may discourage compliance – although pharmacogenetics may in future provide predictive clues. Furthermore, there are physiological and pharmacological synergies that justify the greater effectiveness of drug combinations, and this strategy appears to be that on which the selection of antihypertensive medication may be increasingly based”

Start improving AHTN diagnosis today

(Only for registered medical doctors, register here)

Download DNArterial® Requisition Form: PT | EN

Download DNArterialPLUS® Requisition Form: PT | EN


Go back to products  |  Download Product Sheet  |  Need further information? Contact us

SELECTED REFERENCES

[1] Am Heart J. 2008;156(2):397-404. Gerhard T, Gong Y, Beitelshees AL, Mao X, Lobmeyer MT, Cooper-DeHoff RM, et al. Alpha-adducin polymorphism associated with increased risk of adverse cardiovascular outcomes: results from GENEtic Substudy of the INternational VErapamil SR-trandolapril STudy (INVEST-GENES). [2] Am J Hypertens. 2009;22(2):169-75. Suonsyrja T, Hannila-Handelberg T, Fodstad H, Donner K, Kontula K, Hiltunen TP. Renin-angiotensin system and alpha-adducin gene polymorphisms and their relation to responses to antihypertensive drugs: results from the GENRES study. [3] American Journal of Hypertension. 2011;24(4):392-400. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jr., et al. The Seventh Report of the Joint National Franceschini N, Reiner AP, Heiss G. Recent Findings in the Genetics of Blood Pressure and Hypertension Traits. [4] Ann Med. 2012;44(1):653399. Johnson JA. Advancing management of hypertension through pharmacogenomics. [5] Circulation. 2007;115(6):725-32. Su X, Lee L, Li X, Lv J, Hu Y, Zhan S, et al. Association between angiotensinogen, angiotensin II receptor genes, and blood pressure response to an angiotensin-converting enzyme inhibitor. [6] The Lancet. 2012;380(9859):2224-60. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. [7] Vascul Pharmacol. 2006;44(2):107-18. Arnett DK, Claas SA, Glasser SP. Pharmacogenetics of antihypertensive treatment.