Genetic Association between tumor necrosis factor (TNF-alpha and TNF-beta) gene polymorphisms and inflammatory bowel disease

Abstract

Background: Inflammatory bowel disease (IBD) is associated with chronic inflammation of the endothelial lining of the gut. Although, the exact aetiology is not completely understood, combined genetic and immunological factors appear to promote disease initiation and progression. Several studies associated the illness with single nucleotide polymorphism (SNP) on major immunological cytokines such as TNF-alpha and TNF-beta. Thus, the present study aims to investigate TNF-α and TNF-β genes polymorphisms in cases diagnosed with IBD. Subjects and methods:Genomic DNA isolation was performed on isolated buffy coat layers from peripheral blood of 75 individuals. Candidate SNP locations on TNF-α and TNF-β coding sequences were amplified by PCR and sequenced for SNP identification. Results:Genetic examination of TNF-α and TNF-β allele polymorphism revealed significant association with IBD prevalence and disease manifestation, (p=0.002) and (p<0.001) respectively. GA haplotype frequencies were higher in IBD patients when compared to healthy control, being 29(58%) in TNF-α, and 26(52%) in TNF-β of the studied alleles. Similarly, both GG and AA haplotypes of TNF-α showed a strong association with cases diagnosed with ulcerative colitis but not with Crohn’s disease (p=0.007). Additionally, none of the studied haplotypes of both cytokines showed any association with gender or age groups of the included individuals. ConclusioTNF-α (-308G/A) and TNF-β (+252A/G) sequence analysis revealed that cytokines heterogeneities are associated with IBD susceptibility. Early genetic screening for individuals with familial history could provide a better predictive value for IBD initiation and progression, that would essentially help in early diagnosis, management and prevention.