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Immune Biomarkers and Polymorphisms in Hungarian Asthmatic School-children Population

This study aims to determine immune biomarkers and polymorphisms at the glutathione S-transferase genes in a population of Hungarian school-children with asthma. The study investigates the association between gene polymorphisms and cellular and humoral immune markers in asthma and allergy. The findings suggest a weak to moderate effect of the genetic polymorphisms on immune markers, with an interaction between the GSTM1 and GSTP1 genes. Further investigations are needed to validate these results.

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Immune Biomarkers and Polymorphisms in Hungarian Asthmatic School-children Population

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  1. Determination of immune biomarkers and polymorphisms at the glutathione S-transferase genes in a Hungarian asthmatic school-children population

  2. E. Erdei, B. Schoket, A.Páldy, I.Farkas, P. Rudnai, A. Pintér National Institute of Environmental Health, József Fodor National Center for Public Health, Budapest, Hungary

  3. Introduction • GSTsupergene family: Phase II cytosolic enzymes encoded by 16 genes • Critical role in cellular protection against oxidative stress and xenobiotics • Detoxify a variety of electrophilic compounds (oxidized lipid, DNA, cathecol products) generated by ROS • An increasing number of GST genes are recognized as polymorphic - (altered catalytic activity - increased susceptibility?)

  4. Pollutants EFFICIENT DETOXIFICATION Allergen sensitization Epithelial cell inflammatory response ROS production Normal Atopy Resolution 30-50% POOR DETOXIF- ICATION Immune effector cell recruitment Enhanced absorption of pollutants/ aeroallergens Progression (Persistent inflammation) Release of mediators, cytokines Increased epithelial permeability Epithelial cell damageand shedding Spiteri et al, Allergy 2000:55, Suppl. 61. 15-20

  5. Aim of the study • To explore susceptibility factors to asthmatic/allergic airway inflammation and altered immune reactions related to environmental pollutants • To investigate immunological parameters in association with glutathione S-transferase gene polymorphisms (GSTM1, GSTP1)

  6. Study population • Sensitive school-children population (N=165) 3rd graders, 9-11 years-old • Allergy/asthma and chronic obstructive bronchitis (n=92), questionnaire-based selection, NEHAP Indoor Air Quality project (1998-99)

  7. Methodology • Cellular and humoral immunity characterisation from blood/serum samples; • GSTM1 and GSTP1 Ile105Val genotypes determined by PCR-based methods from white blood cell DNA

  8. Association of genotypes with cellular immune markers

  9. Association of genotypes with humoral immune markers

  10. CONCLUSIONS • Weak to moderate effect of GSTP1 and GSTM1 genetic polymorphisms to immunological markers of the pupils with asthma and/or allergy • Interaction between GSTM1 and GSTP1 genes in association with asthma / allergy status of the pupils • Selection and size of the study population -- further investigations

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