Association of tumor necrosis factor-alpha and -beta gene polymorphisms in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a complex, multifactorial, chronic inflammatory disorder of the gastrointestinal tract in which immune dysregulation caused by genetic and/or environmental factors plays an important role. The aim of this case-control study was to evaluate the association of tumor necrosis factor-alpha (TNF-alpha) (308) and -beta (+ 252) polymorphisms with susceptibility of IBD. A total of 379 Saudi subjects including 179 IBD patients (ulcerative colitis (UC) = 84 and Crohn's disease (CD) = 95) and 200 age-and sex-matched healthy controls were recruited. TNF-alpha and TNF-beta genes were amplified using an amplification refractory mutation systems polymerase chain reaction methodology to detect TNF-alpha (-308) and -beta (+ 252) polymorphisms. The frequency of the GA genotype of TNF-alpha (-308G/A) was higher, and the frequencies of the GG and AA genotypes were significantly lower in IBD patients compared with those in controls, indicating that genotype GA-positive individuals are susceptible to IBD and that the GG and AA genotypes exert a protective effect. The frequency of allele A of TNF-alpha (-308G/A) was significantly higher and that of allele G was lower in IBD patients compared with those in controls, indicating an association of allele A with IBD risk in Saudi patients. On stratification of IBD patients into UC and CD, an almost similar pattern was noticed in both the groups. The results of TNF-beta (+ 252A/G) polymorphisms showed a significant increase in the frequency of the GG genotype in IBD patients, suggesting a positive association of GG genotype with IBD risk. On stratification of IBD patients into UC and CD, the genotype GG of TNF-beta was associated with susceptibility risk to UC but not CD. The frequencies of alleles and genotypes of both TNF-alpha and -beta polymorphisms are not affected by sex or type of IBD (familial or sporadic). TNF-alpha (-308G/A) and TNF-beta (+ 252A/G) polymorphisms are associated with risk of developing IBD in Saudi population.