The TNF-α -308 polymorphism may affect the severity of Crohn's disease

Abstract

OBJECTIVE:The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism.METHODS:This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95% confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease.RESULTS:The low producer predicted phenotype was present in 76.9% of Crohn's disease cases and 75.8% of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03).CONCLUSIONS:The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease.

Inflammatory Bowel Disease: The Association of Inflammatory Cytokine Gene Polymorphisms

“…Available literature on the TNF-α (-308G/ A) polymorphism shows its importance in the pathogenesis of CD and UC [58][59][60]. From the outgoing results, it is clear that allele A and genotype GA of TNF-α (-308G/A) polymorphism are associated with IBD susceptibility in Saudi population.…”

“…TNF-α (-308G/A) polymorphism is reported to be significantly associated with the severity of CD and/or UC in Irish [83], Czech [102], Italian [112], Caucasian patients from New Zealand [128], and Brazilian patients [60]. However, it is not clear whether it is directly involved in pathophysiology of IBD or serve merely as markers in Linkage disequilibrium with susceptibility genes [83].…”

“…Although the frequency of allele G was reported to be slightly higher in Iranian Azeri Turkish IBD patients, it did not reach statistical significance [110]. Further, no association of TNF-α(-308G/A) polymorphism with IBD susceptibility was found in Australian [82], Brazilian [60,130], Canadian [100], Chinese [106,131], Czech [132], French [133], Indian [108], Korean [115], Newfoundland [27], Spanish [126], and Turkish [120] populations. The reason for these differences in the TNF-α genetic associations with IBD etiology might be the variations in sample size, genotyping methods, and/or ethnicity itself as frequencies of alleles and genotypes of TNF-α (-308G/A) also vary in different ethnic healthy populations worldwide [39] ( Table 3).…”

“…The results of these studies on association of TNF-α polymorphism with IBD are not consistent, and variations have been reported [60]. These variations might be due to genetic differences in populations or systemic variations in the ancestry of IBD patients and control subjects involved in the studies [27].…”

Replication of Identified Inflammatory Bowel Diseases Genetic Associations: A Case–Control Study in the Tunisian Population

“…However, other studies that have confirmed evidence for linkage for an IBD susceptibility locus on 6p23 have failed to demonstrate an association to TNFα [36]. Santana et al [37] also showed that TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of CD but may affect the severity of the disease.…”