EBVD – Sub-project

European Biobank on PAD Patients

Abstract

PAD ( Peripheral Arterial Diseases) affects approximately 27 million people in Europe and North America, and it is a strong predictor of morbidity and mortality. Despite advances in clinical management, the pathophysiological basis of PAD is not entirely elucidated. Recently, however, interest has shifted to understanding the genetic variation contributing to common, complex disease where disease risk is polygenic and characterized by environmental factors, and gene-environment interactions. The aim of European Biobank on PAD patients is to establish a new, large, intensively-phenotyped cohort of patients with PAD, as a resource for studying the genetics of peripheral arterial disease. DNA and non-identifiable information from this cohort will be made available to researchers and international collaborators. All PAD participants will be asked to contribute blood samples from which DNA will be extracted and stored for future investigation. The information from the DNA, along with answers to a life-style and medical history questionnaire, clinical and biochemical measurements taken at the time of donation, and subsequent health developments over the life course will be stored and used for research purposes.
Long-term potential outcomes of this research include the targeting of PAD prevention and treatment, and the development of screening tools based on the new genetic information. The project will be able to help the understanding of the different aggressivity both systemic (CHD and/or CVD) and distrectual (from non-symptomatic to CLI).
European Biobank on PAD patients (EBPp) has been accepted as a part of The pan-European Bio Banking and Biomolecular Resources Research Infrastructure ( BBMRI)which is a pan-European and broadly accessible network of existing and de novo biobanks and biomolecular resources.

Background

Peripheral arterial disease (PAD), the most common form of peripheral vascular disease, results from atherosclerotic build up in the peripheral arteries, with clinical manifestations ranging from intermittent claudication (leg pain during exercise) to critical limb ischemia, gangrene, and amputation. PAD affects approximately 27 million people in Europe and North America, and it is a strong predictor of morbidity and mortality. Often asymptomatic and underdiagnosed, the public health significance of PAD should not be underestimated. The risk of death within 10 years is six fold higher for symptomatic and asymptomatic peripheral arterial disease patients compared with patients without peripheral arterial disease.

Risk factors associated with PAD include typical cardiovascular risk factors, such as older age, cigarette smoking, diabetes mellitus, hypercholesterolemia, and hypertension. PAD is also very common in the western world, based on symptoms of intermittent claudication. Despite advances in clinical management, the pathophysiological basis of PAD is not entirely elucidated. Recently, however, interest has shifted to understanding the genetic variation contributing to common, complex disease where disease risk is polygenic and characterized by environmental factors, lifestyle and gene-environment interactions. PAD epitomizes such a disease, and highlights the inherent difficulties in understanding the underlying genetic predisposition to the development of peripheral arterial disease.
The aim of European Biobank on PAD patients is to establish a new, large, intensively-phenotyped cohort of patients with PAD, as a resource for studying the genetics of peripheral arterial disease. DNA and non-identifiable information from this cohort will be made available to researchers and international collaborators.

Project Description

The objectives of the European Biobank on PAD patients are :

• Recruitment. To recruit and phenotype patients with PAD, allowing identification of genetic variants relevant to the pathogenesis of peripheral artery disease.
• Public Understanding. To conduct an early and sustained public consultation programme to understand and explain the public reaction to genetics in atherosclerosis, and their reaction to participation in research.
• Research capacity. To create a multi-institutional collaboration across VAS- Vascular – Independent Research and Education – European Organisation participating centres, that will share knowledge and best practice in the genetics of PAD.
• Exemplar studies. To conduct specific research projects with identified protocols in the areas of PAD in the perspective to widen the researches with future projects on the other vascular diseases (EBVD).

The clinical centres afferent to the VAS network and members of the project will provide biological material and information both of certified quality to support the research in full conformity with the national and international laws on patients’ rights.
The project’s first step has been to define and validate all the procedures shared in the different phases of biological sample collection.
In order to achieve this goal several blood collection operation will take place in European countries on patients who will have signed the informed consent which will be extended to the conservation and the use of the blood for research.
The Consent will be collected on a special form, approved by VAS’ Ethical Committee. The identification of samples will be possible through the attribution of codes and the anonymity will be granted by mean of a specific software.
Contextually with the creation of the biobank, two databases have been created: one to input the data of the biological material, the other to stock the donors’ personal information.
The coordination of the Centres and the biobank will be carried out by VAS Headquarter.
Each centre will receive the instructions for the blood-collection, its conservation and its sending to the biobank. Along with the instruction they will also receive a packaging in conformity with the in-force-laws for biological material transport .
The centres will also be supplied of the kit containing the tubes for blood-collection, the labels with the codes to be put on the tubes and the label to be put on the shipment when the sample is sent to the biobank.
All the patient’s personal and medical information will be input by means of a dedicated portal on anonymous form.
The sample will be sent via international currier and one it arrives at the biobank it will be recorded and stocked.
A special software will monitor each phase of the process, included all the parameters of function of the implants used to stock the samples.
A web-site, by means of which the monitoring and managing of the samples stocked in the biobank can be performed, will be available

Advantage of the European Biobank on Pad Patients

Unlike general population biobank studies, the European Biobank on PAD patients has its main focus on genetic predisposition, lifestyle and the environment associated with PAD.

Inherent advantages

The European population is ideally suited to genetic epidemiological studies of PAD. The overall incidence, prevalence and mortality from PAD are high and premature deaths are relatively common. In addition, Europe has a high prevalence of adverse lifestyle risk factors, which facilitate studies of the interactions between peripheral atherosclerosis, lifestyle and genetic factors. A further advantage of Europe is its relatively stable population.

Unique features of the European Biobank on PAD patients

The European Biobank on PAD patients is one of a growing number of large DNA collections or biobanks across the world. Three important unique characteristics of the European Biobank on PAD patients will be (i) its focus on the genetic predisposition, lifestyle and the environment of PAD, that has been relatively neglected in other studies, and (ii) the ability to link individual data of PAD patients with detailed past and future health records (iii) the formula of a stable and experimented organization suitable for future subprojects of EBVD Biobanks on other vascular diseases.

Utility of the European Biobank on Pad Patients

We have described the constitution of the European Biobank on PAD patients which is the first DNA bank created in Europe by the multi-centre collaborative project for this disease. The Biobank has taken care of ethical aspects since the collection and storage of personal and genetic information follow the indications of the Council of Europe, as stated in the Convention on human rights and biomedicine (Nov 19, 1996), and those of UNESCO, as reported in the Declaration on human genome (Nov 11, 1997). In addition, the handling of personal and genetic data collected follow the indications and norms existing in each participating country.
VAS has already set up a website to allow the partners to share the scientific information and for entry data.
It is the policy of the VAS Research Network to favour further collaborative genetic studies. Other investigators not belonging to the VAS, who would like to have access to the DNA Bank for genetic studies, must submit the study design to the scientific committee represented by the principal investigators of the VAS and must agree to the terms for data publication. Adequate procedures are used to anoniymize personal information and to guarantee confidentiality of genetic results, such as disease genetic predisposition. All results published must not reveal the patient’s identity.

Conclusion

PAD is a complex disorder consequent to genetic predisposition, lifestyle and the environment. A Biobank, biorepository of a large number of DNA samples from PAD patients, together with a database including their personal and clinical data, has a crucial role in the research of PAD. Such an organization favours and stimulates collaborative studies. The constitution of a well organized biobank, an adequate choice with respect to design strategies and improved genotyping methods could greatly enhance the current understanding of the molecular genetic basis of this disease. Finding complex disease genes may allow us to determine which subjects are at risk of PAD before that genetic susceptibility is converted into disease. In addition, the identification of such genes should reveal more about the molecular pathway causing the disease, thus suggesting new and relevant targets including new diagnostic tools and more efficient drug treatment.