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

Abstract

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.

• Authors: Patrick P J van der Veek, Marlies van den Berg, Yvette E de Kroon, Hein W Verspaget, Ad A M Masclee
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 100 Issue 11 Pg. 2510-6 (Nov 2005) ISSN: 0002-9270 [Print] United States
• PMID: 16279907 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

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