Childhood asthma and plasminogen activator inhibitor-1 gene polymorphism

AIM: Bronchial asthma is a frequently encountered chronic inflammatory disease in childhood. With recurrent excaserbations, it leads to significant morbidity and increased hospitalization rates. Moreover it causes a serious economical burden for health systems of the countries. Besides the environmental factors, genetic risk factors are also important in the development process of asthma. Many cytokines play role in the pathogenesis of the disease. Plasminogen activator inhibitor-1 gene (PAI-1) is one of these cytokines. In our study, by determining the polymorphisms in PAI-1, we aimed to denote its possible role as a marker in the diagnostic stage for early diagnosis, directing treatment and prevision of the course of the disease.PATIENTS AND METHODS: Pediatric patients followed and treated in Dokuz Eylul University School of Medicine Pediatric Allergy Department for bronchial asthma with or without family history of atopy, and healthy children for the control group were included in the study. Age, gender, cognation of the parents, skin prick tests, total serum IgE levels of all patients were evaluated. PAI-1 gene polymorphisms were studied in the laboratory of the pediatric genetic departmant (DEGETAM). Patients with asthma were compared with the healthy control group.RESULTS: In the asthma group 64 of the 102 patients (62,7%) were male, 38 patients (37,3%) were female. In the control group 49 of the 101 children (48,5%) were male, 52 children (51,5%) were female. In the group of the asthmatic patients with positive family history for atopy 33 of the 53 patients (62,3%) were male, 20 patients (37,7%) were female. In the group with negative family history for atopy 31 of the 49 patients were male and 18 patients (36,7%) were female. The medium age of the asthmatic patient group was 9,24 years (+/-2,92 years); and the control group was 10,84 years (+/-3,15years). The median age of the asthmatic patients with positive family history for atopy was 9,25 years (+/-3,15 years); with negative family history was 9,22 years (+/-2,69 years). The parental consanguinity rates were the same with 7 patients in each group. In patients with positive family history of atopy, skin prick tests were positive in 29 of the 53 patients, serum total IgE levels were found high in 41 of the 53 patients. In patients with negative family history for atopy 29 of the 49 patients had positive skin prick tests and 26 of the 49 patients had high IgE levels. The group with atopy load in the family history had more patients with high IgE. When alleles of the PAI-1 gene were compared in the patient and control group, 87 children with asthma had 4G allele (85,3%), 15 children had 5G allele (14,7%); in the control group 64 children had 4G allele (63,4%) and 37 children had 5G allele (36,6%). The comparision of the polymorphisms in PAI-1 gene between the groups revealed that in the asthmatic patients 4G/5G polymorphism, in the control group 5G/5G polymorphism were higher. No significant difference was found in the frequency of 4G/4G, 4G/5G ve 5G/5G polymorphisms between the patients with and without atopic family history. In the members of atopic family, the frequency of 4G alleles and 4G/4G and 4G/5G polymorphisms were determined higher. The number of the patients with positive skin prick test and high serum IgE levels were positively correlated with 4G alleles and 4G/4G and 4G/5G polymorphisms. 4G/4G, 4G/5G ve 5G/5G genotypes and skin prick test and high serum IgE levels did not display any significant difference between the two groups.CONCLUSION: The frequency of 4G allele of PAI-1 gene and 4G/4G and 4G/5G polymorphisms was found to be high in children with asthma and their atopic relatives. Although statistical significance was not observed, the frequency of 4G allele and 4G/5G polymorphism was high in patients with positive skin prick test ve elevated tsIgE. Among the patients, the number of children with elevated tsIgE levels was detected to be high in patients with a history of atopy.