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.