Background: Changes in cytokine expression have been frequently found in patients with inflammatory bowel disease (IBD). Cytokine values outside the normal range may be somewhat related to common polymorphisms within cytokine genes.
Objective: The present study was designed to investigate the possible association between polymorphisms within Interleukin IL-4 and IL-10 genes and susceptibility to and clinical features of IBD.
Methods: The study population was composed of 140 healthy controls and 75 patients with IBD (40 patients with Crohn's disease (CD) and 35 patients with ulcerative colitis (UC)). Genotyping was performed using polymerase chain reaction with sequence-specific primers.
Results: Higher frequencies for the C allele of IL-4-590 polymorphism (P < 0.0001; odds ratio [OR], 5.68; 95% confidence interval [95% CI], 3.28-9.83) and for the T allele of IL-4-1098 polymorphism (P = 0.016; OR, 1.83; 95% CI, 1.11-3.02) were observed in the whole group of IBD patients. The IL-4-590 C allele was also significantly overrepresented when IBD patients were subdivided into CD and UC (P < 0.0001; OR, 5.2-6.28). While the IL-4-1098 T allele was present at higher frequencies in patients with UC (P = 0.05; OR, 1.95), but not in CD (P = 0.09). Multiple pairwise comparisons indicated that genotypes of all polymorphisms investigated within IL-4 gene are correlated with IBD, CD, and UC. Haplotype analysis showed that the IL-4-1098/-590 TC haplotype might predispose individuals to IBD, CD, and UC whereas the IL-4-1098/-590 TT and GC haplotypes have a protective effect. On the contrary, neither allele nor genotype frequencies of IL-10 polymorphisms (IL-10-1082 A > G, IL-10-592 A > C, and IL-10-819 T > C) were associated with IBD, CD, or UC.
Conclusions: The present study suggests that IL-4 polymorphisms might play a role in susceptibility to IBD and its major subtypes in the Iranian population.
Keywords: Crohn’s disease; IL-10; IL-4; Th2 cytokines; genetics; inflammatory bowel disease; polymorphisms; ulcerative colitis.