MeDALL (Mechanisms of the Development of ALLergy; EU FP7‐CP‐IP; Project No: 261357; 2010–2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large‐scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy‐related diseases. To complement the population‐based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.
The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. The corresponding author had full access to all study data and had final responsibility for the decision to submit for publication. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.
Objectives. To study the role of the ADRB2 gene polymorphism (rs1042713) in the impaired external respiratory function in children with bronchial asthma (BA). Material and methods. The study group included 60 children aged 3-17 years with allergic (n=37) and mixed form of BA (n=23). The genotyping of the investigated gene locus was performed by PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism), BA control was exercised using the Asthma Control Test (ACT). Results. The analysis of allele frequencies showed an association of allele A with normal spirogram parameters in patients with BA (p=0.042). In children under 12 years, there were statistically significant differences in spirogram indices when comparing patients with genotypes AA and GG (p=0.045). An association of allele A with the absence of pathological changes was revealed when evaluating the results of spirometry (p=0.021). There was a moderate positive correlation (r=0.615, p=0.011) between the assessment of nocturnal symptoms (Asthma Control Test) and the genotype of the ADRB2 gene polymorphism in children aged 12 years and older. Conclusions. An association of the ADRΒ2 gene polymorphism (rs1042713) with the external respiratory function was revealed in an objective study by spirometry and a subjective assessment of this indicator by the patient himself/herself or by his/her parents. This gene locus can be included in the BA target panel in order to determine the likelihood of uncontrolled course development of the disease with impaired external respiratory function and in the future to develop an individual program for dispensary observation of the patient.
Objective. The role of the GLCCI1 gene polymorphism (rs37973) analysis in children with bronchial asthma (BA). Methods. The study involved 60 children 3-17 years old with allergic (n=37) and mixed forms of BA (n=23). The genetic study included performing genotyping of the studied locus of the GLCCI1 gene (rs37973) by PCR-RFLP (polymerase chain reaction – restriction fragment length polymorphism). Results. Analysis of the frequency of genotypes and alleles occurrence established the predominance of heterozygotes (AG) and allele G in the study group. There were statistically significantly higher indices of VC, FVC, FEV1 and MEF75 (according to spirometry data) with a heterozygous genotype (AG) in comparison with a homozygous GG (p<0,05). At the same time, there was a statistically significantly greater number of children with a FEV1 level ≥80% (p=0,009) when comparing the same subgroups of genotypes. Conclusion. The study revealed the association of GLCCI1 gene polymorphism (rs37973) with the respiratory function according to spirometry data. The presence of a heterozygous gene variant (AG) determined higher indicators of the function of respiratory function (VC, FVC, FEV1, MEF75). The study with the establishment of the GLCCI1 gene (rs37973) genotype can be used to diagnose a prognostically favorable and unfavorable course of asthma in children, which should be taken into account when choosing various basic methods of therapy and rehabilitation.
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