Tumour necrosis factor-α gene -308 G>A and -238 G>A polymorphisms are associated with susceptibility to irritable bowel syndrome and drug efficacy in children.

Abstract

An imbalance in the genetically controlled pro- and anti-inflammatory cytokine production could potentially promote ongoing low-grade inflammation following an episode of acute gastroenteritis and, subsequently, could result in irritable bowel syndrome (IBS; post-infectious IBS, PI-IBS). Since there is very little known on the impact of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) on IBS, we conducted the present study with aims of determining the correlation between TNF-α gene polymorphisms (-308 G>A and -238 G>A) and susceptibility to IBS and drug efficacy in children. Diarrhoea-predominant IBS patients and healthy subjects were recruited for DNA extraction. The genotypes were tested using polymerase chain reaction-restriction fragment length polymorphism. In addition to conventional symptomatic treatments, Live Combined Bifidobacterium, Lactobacillus and Enterococcus Powder and Montmorillonite Powder were administered to all the patients participating in the study for consecutive 4weeks. The efficacy was evaluated 2weeks after the withdrawal of the drugs. The association between gene polymorphism and drug efficacy was analysed by means of binary logistic regression analysis. Patients in the IBS group were susceptible to IBS with GA genotype and A allele of -308 G>A so were those with AA genotype and A allele of -238 G>A. The symptoms were also alleviated following treatment. The cure rate of patients with GA genotype of -308 G>A and AA genotype of -238 G>A was low. These findings suggested that the haplotype AA could potentially be associated with the cure rate of IBS patients. GA genotype of -308 G>A, AA genotype of -238 G>A, enterobacteria and 5-hydroxytryptamine in serum may act adversely, whereas bifidobacterial may be beneficial to the efficacy of IBS treatment. The above findings evidently suggest that the frequency of TNF-α gene -308 G>A carrying GA genotype and A allele and -238 G>A carrying AA genotype and A allele is higher in children with IBS. Additionally, GA genotype of -308 G>A and AA genotype of -238 G>A may act adversely to the efficacy of IBS treatment, which may be a reference index for predicting the curative effect of IBS.