Proinflammatory cytokine gene polymorphisms in irritable bowel syndrome.
BACKGROUND
Irritable bowel syndrome (IBS) is a multifactorial functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. Proinflammatory cytokines can play an important role in intestinal inflammation, while their production is under genetic control.


METHODS
This study was performed in a group of patients with IBS to analyze the genotype frequencies of a number polymorphic genes coding for proinflammatory cytokine (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-alpha), and IL-1 group). Using polymerase chain reaction with sequence-specific primers method, the cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS were detected on gel electrophoresis, and the results were compared with healthy control subjects.


RESULTS
Results of the analyzed data showed that the frequencies IL-1R C allele at position Pst-I 1970 (P = 0.017), IL-6 G allele at position -174 (P = 0.002), and TNF-alpha G allele at position -238 (P < 0.001) in the patient group were significantly higher than the control group. IL-6 GG genotype (-174) and TNF-alpha GG genotype (-238) in the patient group were also significantly overrepresented (P < 0.001), while IL-6 CG genotype (-174) and TNF-alpha GA genotype (-238) were significantly decreased in the patients with IBS (P < 0.001). The frequencies of IL-6 (-174, nt565) GG haplotype and TNF-alpha (-308, -238) GG haplotype were also significantly higher in the patient group (P < 0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-alpha GA were significantly decreased in the patients with IBS (P < 0.001).


CONCLUSIONS
IL-6 and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual susceptibility to IBS and might have a role in pathophysiology of disease.
Department of Gastroenterology and Hepatology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Elham
E
Barkhordari
Nima
N
Rezaei
Bita
B
Ansaripour
Pegah
P
Larki
Maryam
M
Alighardashi
Hamid Reza
HR
Ahmadi-Ashtiani
Mahdi
M
Mahmoudi
Mohammad-Reza
MR
Keramati
Peiman
P
Habibollahi
Mohammad
M
Bashashati
Naser
N
Ebrahimi-Daryani
Ali Akbar
AA
Amirzargar
D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D007492:Iran; D043183:Irritable Bowel Syndrome / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha