Genetic susceptibility to asthma in children

Abstract

Introduction: Bronchial asthma is a chronic inflammatory disease based on an inappropriate stimulation of the immune system, for instance by environmental aeroallergens. It is characterized by bronchial hyperreactivity, reversible airway obstruction and mucus overproduction. During the last decades bronchial asthma has become the most common disease of childhood. Accordingly, many epidemiological and genetic studies have dealt with its origin. In fact, hundreds of genome-wide linkage analyses and association studies have identified several chromosomal regions harboring asthma susceptibility genes like chromosome 2q, 5q, 6q, 1 lq, 12q and 13q. Also about 100 candidate genes for asthma have been described. However, not all of them have been confirmed in independent studies. Besides the genetic predisposition environmental factors play an important role in the development of allergic diseases. Thus, recent studies focused also on the interaction of genes variants with environmental factors which is summarized under the term genetic epidemiology. Purpose and Objectives: To evaluate peculiarities of functionally compromised alleles and genotypes spread of the CC16 gene in the general population sample of Moldovans; to assess the frequencies of alleles and genotypes of the CC16 genes in children with asthma and healthy controls; to study the association of genetic polymorphisms with asthma phenotypes; to evaluate the risk of childhood asthma development under the influence of the gene-environment interactions; to develop prognostic methods for the asthma onset and clinical evolution assessment in children. Material and methods: The project is based on 15 children with asthma, in which we collected the history, including allergy history and collateral history, in order to build their pedigrees. We performed meta-analysis which reveals the connection between mutant allele of CC16 gene and asthma’s phenotype. Results: The study findings reveal aspects of the pathogenetic mechanisms of multifactorial disease development in ethnic Moldavians. The elaborated prognostic algorithm allows identifying high risk subjects for atopy and asthma development. The study revealed peculiarities of the spread of asthma candidate genes in children of Moldovan ethnicity and identified genetic markers and their combinations that potentially increase the risk of asthma development and are associated with clinical phenotypes of the disease. Conclusion: Particular genetic variants of the asthma candidate gene CC16 in Moldovan children were assessed; the role of genetic factors and gene-gene interactions in the asthma development was determined; unfavorable genetic variants for the asthma development and evolution in native population were identified.