Novel Gentic Variations Contributing to Asthma Susceptability in Saudi Arabia
Novel Gentic Variations Contributing to Asthma Susceptability in Saudi Arabia
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.
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 β-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.