In 2012, more than 2 million Canadians aged 12 years and older were asthmatic. Asthma is a chronic respiratory disease characterised by three key components: (1) obstruction and (2) inflammation of the airways, and (3) bronchial hyperactivity. Clinical symptoms include dyspnea, cough, and wheezing. Asthma is a complex trait with multiple genetic and environmental factors interacting to dictate disease pathogenesis. Air pollution (indoor and outdoor) and allergens (i.e. animal/pet danders, pollen, and dust) are some of the known environmental factors which can influence the development and severity of asthma.
Prof. Laprise established an asthma biobank to archive a collection of 1,448 DNA samples in 254 extended families. The biobank is unique in the genetic characteristics of the recruited families. The proband of a recruited family must be an asthmatic individual with 4 French Canadian grandparents. A recruited family in the collection has between 3 to 17 family members and the number of affected individuals within the family ranges from 1 to 10. The respiratory health of the participants was evaluated according to the American Thoracic Society. (i.e. metacholine test, lung function tests, and skin prick test). Seriological data (i.e. cell counts and serum IgE levels) and medical history were gathered and documented. Gentoypes of more than 610,000 genetic polymorphisms, determined previously using the Illumina 610K microarry for a genome wide association study, are available for 1,214 subjects. (Genes Immun. 2014 Mar 20)
A new recruiting process began in 2015 for 215 individuals included in the biobank, from which purified cell samples of eosinophils and naives CD4+ T lymphocytes were obtained. Methylation analysis by Methyl-capture sequencing and transcriptome analysis by sequencing were performed on both cell types. A new assessment of the condition of these participants (respiratory, skin prick test, medical history, etc.) is ongoing. The biobank now has longitudinal data for a group of the participants originally recruited.
Canadian Institute for health research
Resolving Systems Epigenomes of T-cells in Autoimmune and Inflammatory Diseases (Co-principal chercheur: Tomi Pastinen)
A Three-Generation Canadian Study (CAN-3-GEN) on the Developmental Origins of Health and Disease (Chercheur principal: Malcolm Sears)
Genomic risk in asthma susceptibility accessed by next-generation integrative tools (Co-principal chercheur: Tomi Pastinen)
Projet équipe CEEHRC: Epigenetic mechanisms for the development of asthma (Chercheurs: Celia Greenwood, Catherine Laprise, Michael Kobor, Peter Paré, Anita Kozyrsky, Andrew Sandford, Aurélie Labbé, et Denise Daley)
Ongoing research projects
- Longitudinal study of the methylome and the respiratory condition of a sub-group of the familial asthma cohort of Saguenay-Lac-St-Jean
- Expression study of bronchial tissue following bronchial thermoplasty in severe asthmatic individuals (Collaborators: Jamila Chakir, Michel Laviolette)
- Methylome and transcriptome of CD4+ T lymphocytes and eosinophils in the 17q12-21 region in asthma (Collaborator: Dr Tomi Pastinen)
- Methylome of CD4+ lymphocytes in the familial asthma cohort of Saguenay-Lac-St-Jean (Collaborators: Dr Tomi Pastinen)
- Eosinophils in asthma and allergy: caracterisation of epigenome and transcriptome (Collaborators: Dr Tomi Pastinen)
- Integrative study of genetics and epigenetics in allergic asthma (Collaborators : Emmanuelle Bouzigon, Florence Demenais, Mark Lathrop, and Tomi Pastinen)
- Functional study of ALOX15 as a potential therapeutic target in allergic asthma (Collaborators: Céline Bergeron, Élyse Bissonnette, Marie-Renée Blanchet, Inuk Bossé, Yohan Bossé, Louis-Philippe Boulet, Jamila Chakir, Qutayba Hamid, Nicolas Flamant, Michel Laviolette, Jean-Pierre Lavoie, Karim Magni, and David Marsolais)
Clinical manifestations from food allergies include rash, angioedema, rhinoconjunctivitis, voice change, bronchospam, vomiting, abdominal cramp, diarrhea, and/or anaphylactic shock. Peanut allergy is the principal cause of fatal anaphylactic shocks and its incidence has been increasing in the past 20 years. It is estimated that 1.1% or 3 million Americans are allergic to peanuts (including nuts). An allergic reaction occurs when the immune system produces immunoglobulin E (IgE) against specific proteins (eg: from food). When IgE comes in contact with these specific proteins, the mast cells are then signalled to release several inflammatory mediators including histamine, which elicit various clinical manifestations aforementioned. At present food allergies have no cures; however, several studies have reported genetic variants associated with peanut allergy. Hence, it is believed that peanut allergy is likely influenced by genetic and environmental factors.
Completed research project
As part of a large initiative of Allergen Excellence Network and a follow-up study of the work done by the CanGoFar research project, a case-control genetic association study was performed for HLADQ-B1 in relation to its association with peanut allergy. This project identified two allelic forms of HLADQ-B1 associated with peanut allergy (Eur J Hum Genet. 2013 Oct;21(10):1181-4). These findings will significantly impact peanut allergy prevention and management.
Ongoing research projects
- Creation of an oral desensibilisation clinic to food allergens for kids (Collaborators: Dr Philippe Bégin, Dr Charles Morin)