Association of -308G/A Polymorphism and Serum Level of TNF- α with Bronchial asthma in Children

Abstract

Genetic polymorphism of Tumor necrosis factor alpha (TNF-α)-308 G/A is one of the potential markers involved in bronchial asthma pathogenesis. This highly polymorphic gene can influence TNF-α serum levels which has major biological effects on airway inflammation, remodeling, and hyper responsiveness. This study was designed to evaluate the association between TNF-α-308 G/A polymorphism, serum levels of TNF-α and the susceptibility to bronchial asthma in children. The study included 102 pediatric patients with bronchial asthma recruited from Pediatric Allergy and Pulmonology Clinic, Specialized Pediatric Beni Suef University Hospital. Bronchial asthma was classified according to Global Initiative for Asthma (GINA) Guidelines. Moreover, 104 healthy age and sex matched children were enrolled as normal control. Serum TNF-α was measured by ELISA. Analysis of TNF-alpha G308A Polymorphisms was done by allele- specific Polymerase Chain Reaction (PCR). TNF-α level was significantly higher in bronchial asthma patients when compared with the control group, p value 0.001. Individuals with mutant genotype (GA and AA) expressed higher levels of serum TNF-α in comparison to the wild type GG carriers, P value 0.01. The GA genotype frequency of TNF-α-308 G > A polymorphism was significantly higher in patients (34.3%) than (vs.) controls (21.2%) P value 0.028, OR = 2.04; 95% CI = 1.11-3.84. The frequency of combined (AA + GA) genotypes showed a significant difference among cases in comparison with the controls (41.2% vs. 26%), p value 0.027. The pooled OR was 1.99(95% CI=1.1-3.6). In the same context, the A allele was significantly more frequent in asthmatic patients (24%) vs. control (15.4%), P value 0.035 (OR = 1.74, 95% CI = 1.05-2.8) which demonstrated an evidence of possible association between TNF-α-308 G/A polymorphism and bronchial asthma. We concluded that TNF-alpha genetic polymorphisms could have a role in the development of bronchial asthma among Egyptian children.