Association of promoter region polymorhism of the tnfб gene with the development of atopic bronchial asthma

Atopic bronchial asthma (ABA) is a complex genetic disease characterized by increased airway responsiveness to a variety of stimuli, reversible airway obstruction, and airway inflammation. The genetic polymorphisms -238 A/G and -308 A/G of the TNFA gene were studied by PCR-RFLP analysis in the group of asthmatic patients with age of manifestation before 18 years (83) and the population group (117). According to obtained data the frequency of -238A allele of the TNFA gene was significantly lower in the group of patients with ABA (1,2%) as compared to the population group (5,6%). The analysis of distribution of the G -308A polymorphism of the TNFA gene revealed significant increase of the frequency of -308A allele in the patients with ABA (9,0%) as compared to the population (4,0%). According to odds ratio the careers of -308A allele of the TNFA gene have 2-fold increased risk of the development of ABA (OR = 2,48; CI: 1,06-5,82). The frequency of -308A allele of the TNFA gene in the group of patients was significantly higher in women (14,8 %) as compared to men (2,6 %, p = 0,0064, df = 1). After comparing the distribution of genotypes of -238 and -308 polymorphisms of the TNFA gene together significant difference between patients with ABA and population was observed. Combined genotype -238A/G + -308G/G of the TNFA gene associated with the lowest level of gene expression resulted in considerable decrease of ABA risk (OR = 0,097). Different hypotheses of the role of polymorphic variants of the TNFA gene in pathogenesis of ABA were discussed.

ГЕНЕТИЧЕСКАЯ ПРЕДРАСПОЛОЖЕННОСТЬ, полиморфизм, ассоциация, ГЕН TNFA, мультифакториальные заболевания, АСТМА