Association between polymorphisms within tumor necrosis factor genes and the development of bronchial asthma among Egyptian children

ABSTRACT

Tumor necrosis factor [TNF] is a proinflammatory cytokine that is eminently important in the pathogenesis of bronchial asthma. Bronchial asthma is a frequent respiratory disease characterized by variable airflow obstruction, inflammation of the airways, and bronchial hyper-responsiveness [BHR]. In an effort to find out the polymorphism[s] in genes whose variant[s] have been implicated in asthma phenotypes, we examined the genetic effects of TNF [TNFA and TNFB] polymorphisms on the Egyptian asthmatic children. In this study, skin prick test [SPT], total IgE level, pulmonary functions including FVC, PEF, FEV[1] and FEF[25-75], and bronchial asthma hyper-responsiveness [BHR], were investigated. Sixty asthmatic subjects, as defined by standard MRC respiratory questionnaire, plus 40 healthy controls were genotyped for two common single-nucleotide polymorphisms [SNP] using enzymatic digestion of polymerase chain reaction [PCR]. Asthma was significantly more common in subjects with TNFA-1031C>T [P= 0.007]. Although the SNP containing TNFB+252A>G polymorphism might seem to be excluded in our sample as a cause of the disease [P= 0.6], it was in a very strong linkage disequilibrium with TNFA-1031C>T [P= 0.000002]. All the TNFA-1031C>T genotypes were in a strong association with the severity of the asthma. Incidentally, the LT alpha Ncol-AA [80%] was the most predominant genotype with the severe form. However, someone might predict the severity of asthma and consequently the phenotype of an asthmatic individual by knowing the polymorphism of either the TNFA-1031C>T or even the LT alpha Ncol. These findings may have implications for future early intervention studies by helping to identify infants at increased risk for childhood asthma