title: The impact of common tumor necrosis factor haplotypes on the development of asthma in children: an Egyptian model.
abstract: Conflicting results have arisen among different ethnic populations with regard to the ability of tumor necrosis factor (TNF) to control the development of bronchial asthma. We examined common TNF polymorphisms (TNFA -1031C>T, TNFA -308G>A, and TNFB +252A>G) to develop a model of the associations between these genetic markers and the development of the disease in Egypt. Amplified DNA from buccal mucosa was genotyped for 240 children using polymerase chain reaction-restriction fragment length polymorphism. Skin prick test, total serum immunoglobulin E levels, and assessment of pulmonary functions were investigated. The onset age for one-third of the asthma patients in our study was between 7 and 10 years. The TNFA -1031C>T and TNFA -308G>A polymorphisms were strongly associated with the risk of asthma (p = 0.007, and p = 0.000, respectively), but the TNFB +252A>G polymorphism was not (p = 0.6). We detected a significant linkage between the +252A>G and -1031C>T, and another between the +252A>G and the -308G>A (p < 0.0001 for both). The -1031C>T and -308G>A polymorphisms were not linked (p = 0.14). The -308A/A genotype was absent, and the -308A allele was expressed only in patients with -308G/A heterozygosity (13%). All but the +252G/A genotype were also strongly associated with the severity of disease. Environmental factors, as genetic variations, clearly influence susceptibility, the onset, progression, and severity of bronchial asthma. More information is needed to develop genetic models of susceptibility for different ethnic populations.
authors.affiliation: Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdul-Aziz University, Jeddah, Saudi Arabia.
authors.forename: Essam H
authors.initials: EH
authors.lastname: Jiffri
authors.forename: Nasser A
authors.initials: NA
authors.lastname: Elhawary
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004534:Egypt; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007223:Infant; D008172:Lung Diseases, Fungal; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha