Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome

Am J Gastroenterol. 2005 Nov;100(11):2510-6. doi: 10.1111/j.1572-0241.2005.00257.x.


Objectives: Imbalances in the genetically controlled pro- and anti-inflammatory cytokine production may promote ongoing low-grade inflammation after an acute gastroenteritis, and subsequently, irritable bowel syndrome (IBS) (post-infectious IBS, PI-IBS). We studied gene promoter single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNF-alpha, pro-inflammatory) and interleukin-10 (IL-10, anti-inflammatory) in IBS patients and controls.

Methods: DNA was extracted from peripheral blood leucocytes of 111 IBS patients and 162 healthy controls. Genotype and allele frequencies were assessed by analyzing SNPs at position -308 (TNF-alpha) and -1082 and -819 (IL-10).

Results: Homozygous high producers for TNF-alpha (A/A) were rare (overall prevalence 2.6%). The heterozygous TNF-alpha genotype (G/A, high producer) was significantly more prevalent in IBS compared to controls (41%vs 26%, p= 0.02). More patients (41%) than controls (30%) were positive for the A allele (p= 0.044; odds ratio (OR) 1.68, 95% confidence interval (CI) 1.01-2.79), with a similar trend for diarrhea (54%) versus constipation and alternating subtypes (<33%, p= 0.079), but not for subgroups according to a history of acute gastroenteritis. IL-10 genotypes were similarly distributed in patients and controls for both SNPs. Possession of a high producer TNF-alpha and a low producer IL-10 genotype were significantly more prevalent in IBS (9%) versus controls (3%, p= 0.035; OR 3.11, 95% CI 1.03-9.36) and in diarrhea (20%) compared to other IBS subtypes (<4%, p= 0.026).

Conclusions: Our results support the emerging hypothesis that genetically determined immune activity plays a role in the pathophysiology of IBS. Future studies in larger, clinically relevant, IBS subgroups are warranted to establish definite associations with cytokine gene polymorphisms.

Publication types

  • Comparative Study

MeSH terms

  • Adenine
  • Adult
  • Constipation / genetics
  • Constipation / physiopathology
  • Diarrhea / genetics
  • Diarrhea / physiopathology
  • Female
  • Gastroenteritis / complications
  • Gene Frequency
  • Genotype
  • Guanine
  • Heterozygote
  • Homozygote
  • Humans
  • Inflammation Mediators
  • Interleukin-10 / genetics*
  • Irritable Bowel Syndrome / genetics
  • Irritable Bowel Syndrome / immunology*
  • Irritable Bowel Syndrome / physiopathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics
  • Tumor Necrosis Factor-alpha / genetics*


  • Inflammation Mediators
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Guanine
  • Adenine