Collection of Clinical Data That Will be Used in This Study and Will Form a Data Bank for Asthma in Saudi Arabia Clinical Trial
Official title:
Novel Gentic Variations Contributing to Asthma Susceptability in Saudi Arabia
| Verified date | April 2014 |
| Source | King Saud University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | Saudi Arabia: Research Advisory Council |
| Study type | Observational |
Research Problem Asthma is one of the most common chronic diseases in the world that affects
approximately 300 million individuals worldwide. It is characterized by airway inflammation
and bronchoconstriction leading to airflow obstruction, however, the triggering factors
behind asthma development remains to be elucidated. Genetic risk factors have been suggested
to play a central role in asthma development. Twin studies supported a strong genetic
component to asthma, especially childhood asthma, with heritability estimates suggesting
that 48-70% of asthma risk is attributed to genetic risk factors. Suggestive susceptibility
genes have been identified in European and American populations but not yet in the Middle
East including Saudi Arabia. Identified genes whether they are polymorphic variants of genes
encoding known pathophysiological molecules or novel genes identified by linkage or
genome-wide association studies (GWAS) are inconsistent in different populations thereby
adding to the need to undertake genetic studies on different ethnic populations and in
different countries. Here, the investigators hypothesize that polymorphic variation of novel
susceptibility genes form a major risk factor for asthma development, response to treatment
and progression in the Saudi population with strong diagnostic, prognostic and therapeutic
implications.
Research Significance Since the manifestation of complex inflammatory disorders with strong
heritability is complex involving genetic and environmental interaction, each ethnically
distinct population must be examined to know whether gene-disease association exists in that
population. The objectives of this proposal are to discover novel asthma susceptibility
genes in the Saudi population. A better understanding of the genetic mechanisms of asthma
will enhance our knowledge of its pathophysiology. Asthmatic patients with distinct
genotypes respond differently to asthma medications. Therefore, improvements in diagnostics
and pharmacogenetics may be the first clinical developments of these extensive studies. This
embraces the concept of asthma subphenotypes and stratified medicine where interventions are
targeted at those individuals who will best benefit from them with minimal side effects.
Physicians looking after asthmatic patients will be able to provide better medical service
tailored to those patients, as well as to identify Saudi people at high risk for the
development of asthma, especially the more severe forms of the disease.
Research Objectives The main objective of our proposal is to identify known and novel asthma
susceptibility genes in the Saudi population and to investigate their interaction with
clinical, environmental, and inflammatory factors contributing to asthma pathophysiology.
Research Methodology In this proposal, the investigators will investigate the genetic
factors contributing to asthma susceptibility by determining in Saudi population, the
presence of single nucleotide polymorphisms (SNPs) that have been previously reported from
linkage and GWAS in other populations. Whole genome DNA will also be scanned for novel SNPs
of selected "asthma genes" using microarrays. This will enable us to identify new SNPs that
contribute to the risk of asthma specifically in the Saudi population. In addition, the
investigators will cross-reference all genetic and immunological parameters with the
corresponding clinical data in order to elucidate the impact of certain genes, or their
products (e.g. cytokines), on the clinical manifestation of asthma.
| Status | Completed |
| Enrollment | 2000 |
| Est. completion date | September 2013 |
| Est. primary completion date | September 2013 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 3 Years and older |
| Eligibility |
Inclusion Criteria: 1. Subjects with documented clinical history of asthma for a period of at least 6 months prior to study entry (and a minimum of one clinic follow-up visit since initial diagnosis) 2. Willing to provide written informed consent and in the judgment of the investigator, individuals who are able to understand the informed consent process. 3. Subjects with documented clinical history (in preceding 12 months) of airway reversibility of at least 12% based on Forced Expiratory Volume (FEV1), measured pre and post inhalation of a ß-2 agonist (2 puffs of albuterol using a measured dose inhaler with spacer) OR 4. Individuals demonstrating airway 12% reversibility during recruitment testing and asthmatic symptoms, but with no prior history of asthma and not on an asthma treatment plan, can be recruited as affected individuals if in the opinion of the investigator the individuals are truly asthmatic and have no confounding factors that could explain the reversibility and symptoms. 7. Individuals with strong history of asthma but with waning, or no current symptoms may be included in the study if their asthma was well controlled using an asthma medication. Principal investigator must verify or know the clinical history of an individual before accepting him as an asthmatic individual. 8. Individuals with positive history of asthma but no asthma medication usage and with family history of asthma should be considered for inclusion as cases in the study only if other family members are being recruited. 9. Able to perform Spirometry/FEV1 correctly (only for those above 7years). Exclusion Criteria: 1. Age < 3 years 2. Smoking for 20 years, 1 pack/day or more. 3. Congestive heart failure. 4. COPD. 5. Chronic lung disease other than asthma and COPD. 6. Bronchiectasis. |
Observational Model: Cohort, Time Perspective: Prospective
| Country | Name | City | State |
|---|---|---|---|
| Saudi Arabia | King Khalid University Hospital, College of Medicne, King saud University | Riyadh | Central |
| Lead Sponsor | Collaborator |
|---|---|
| King Saud University |
Saudi Arabia,
Al-Khayyat AI, Al-Anazi M, Warsy A, Vazquez-Tello A, Alamri AM, Halwani R, Alangari A, Al-Frayh A, Hamid Q, Al-Muhsen S. T1 and T2 ADAM33 single nucleotide polymorphisms and the risk of childhood asthma in a Saudi Arabian population: a pilot study. Ann Sa — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | IL-4 receptor alpha and STAT6 single nucleotide polymorphisms are associated with increased risk of asthma in a Saudi Arabian population. | IL-4Ra rs1805010 and rs1801275 SNPs have been found to be significantly associated with asthma susceptibility in different ethnic groups; some STAT6 SNPs, including rs324011 and rs324015, have also been associated with asthma predisposition and/or IgE levels. Risk evaluations of IL-4Ra and STAT6 SNPs in association with asthma have never been evaluated in Saudi Arabian populations. Methods: Saudi Arabian patients with documented history of severe asthma (n=190) and healthy subjects (n=194) were recruited. Allelic and genotype association to asthma was assessed for IL-4Ra and STAT6 polymorphisms using nucleotide sequencing. Results: The IL4Ra rs1801275 SNP A/G-G/G genotypes, but not the A/A genotype, were significantly associated with asthma predisposition (OR=0.47; 95% CI=0.31-0.72; P<0.001*; dominant model); Similarly, for STAT6 rs324011, odds were significantly higher that homozygous T/T genotype could be associated with asthma. | 2 years | No |