TNF-alpha polymorphisms as a potential modifier gene in the cystic fibrosis

Abstract

Modifier genes, as the TNF-alpha gene, can modulate the cystic fibrosis (CF) severity. Thus, -238G> A and -308G> A polymorphisms of TNF-a gene were analyzed as modifiers of CF. In this context, the present study enrolled 49 CF patients (diagnosis performed by sweat test and complete CFTR screening). The -238G> A polymorphism analysis was performed by ARMS-PCR, and -308G> A, by PCR-RFLP. In our data, the -238G> A polymorphism was not associated with clinical variability. The AA genotype for -308G> A polymorphism was a risk factor for early gastrointestinal symptoms (OR= 5.98, 95% CI= 1.06-49.68) and protection for the first Pseudomonas aeruginosa (OR= 0.05, 95% CI= 0.0003-0.007). For the first P. aeruginosa, GA genotype was a risk factor (OR= 10.2, 95% CI= 1.86-84.09); for the same genotype, the diagnosis was made in minor time than the AA genotype (p= 0.031). Considering the -308G> A polymorphism alleles, the G allele was a risk factor for early pulmonary symptoms (OR= 3.81, 95% CI= 1.13-12.97) and P. aeruginosa (OR= 66.77, 95% CI= 15.18-482.7); however, the same allele showed better transcutaneous oxygen saturation (OR= 9.24, 95% CI= 1.53-206.1). The A allele was a protective factor for early pulmonary symptoms (OR= 12.26, 95% CI= 0.08-0.89) and P. aeruginosa (OR= 12.15, 95% CI= 0002-0007), however, the same allele was a risk factor for worst transcutaneous oxygen saturation (OR= 7.01, 95% CI= 1.14-157.4). As conclusion, the -308G> A polymorphism of the TNF-alpha gene was associated with the CF severity.