| Abstract [eng] |
Preschool wheezing syndrome is a common and complex health problem, affecting more than 50% of children under six years of age. Research highlights the importance of genetic factors in the risk of wheezing, and long-term prognoses suggest the possible development of bronchial asthma or other respiratory diseases, possibly even COPD. Efforts to identify phenotypes and endotypes are critical for personalised medicine and effective disease management. Alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic disorder associated with chronic obstructive pulmonary disease (COPD). Its production is determined by the SERPINA1 gene. In this context, studies on the SERPINA1 genotype and its association with wheezing phenotypes are essential. Therefore, the aim of this study was to investigate the frequency of alpha-1 antitrypsin genotypes and SERPINA1 gene polymorphisms in the ALSPAC population-based cohort of long-term follow-up and the PresWeezAging LT, a specialised cohort of Lithuanian preschool children with wheezing syndrome, and to assess the association of wheezing syndrome with the prevalence of bronchial asthma and chronic obstructive pulmonary disease. We found that variants in AAT genotypes are associated with the risk of developing a particular wheezing phenotype and may actively predispose the evolution of wheezing syndrome into bronchial asthma in adolescence. The Pi*Z and Pi*S genotypes were analysed and the Pi*Z genotype frequency in the group of wheezing children (44.8%) was significantly higher than in the control group (20.27%). It was also observed that the control group had more Pi*S variants possibly associated with other pathologies. Furthermore, the results showed that the distribution of Pi*S and Pi*Z alleles in wheezing children was similar to the frequencies observed in COPD patients. Future studies should focus on monitoring cohorts of children and their genetic variations in order to develop preventive strategies and early intervention methods. This could significantly improve the respiratory health of children with genetic AAT mutations and ensure healthy ageing in line with WHO priorities. |
