Cytokine (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies

Genes Immun. 2000 Feb;1(3):185-90. doi: 10.1038/sj.gene.6363657.


The influence of biallelic polymorphisms in the tumour necrosis factor-alpha (TNF alpha), lymphotoxin-alpha (LT alpha) and interleukin-10 (IL-10) genes on stimulated TNF alpha and IL-10 production was studied in ulcerative colitis (UC) patients, Crohn's disease (CD) patients and in healthy controls. A polymerase chain reaction sequence-specific primer (PCR-SSP) system was developed to type nine biallelic polymorphisms, three in each of the TNF alpha, LT alpha and IL-10 genes. Production of the TNF alpha and IL-10 was measured by ELISA in lipopolysaccharide (LPS) stimulated whole blood. Four haplotypes of the TNF alpha gene, three haplotypes of LT alpha and three haplotypes of IL-10 were identified. No significant differences in haplotype frequencies were found between patients and controls overall. On subgroup analysis however, haplotype TNF-2 was more frequent in women with extensive colitis compared to distal colitis (31% vs 12%; P = 0.028). This difference was even greater for the combined TNF-2-LT alpha-2 haplotype (56% vs 21%; P = 0.0007). The TNF-2 and LT alpha-2 haplotypes were associated with higher TNF alpha production in CD patients, and the TNF-4 haplotype was associated with lower TNF alpha production in UC patients. The A allele in the IL-10 promoter region at position -1082 was associated with decreased IL-10 production in CD patients and controls (P = 0.005, P = 0.015 respectively). These data provide evidence that the effect of TNF alpha, LT alpha and IL-10 gene polymorphisms on cytokine production differ in CD, UC patients and controls.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / immunology*
  • Crohn Disease / drug therapy
  • Crohn Disease / genetics*
  • Crohn Disease / immunology*
  • Cytokines / biosynthesis*
  • Cytokines / genetics*
  • Female
  • Gene Frequency
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Lymphotoxin-alpha / biosynthesis
  • Lymphotoxin-alpha / genetics
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Smoking / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics


  • Cytokines
  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha
  • Interleukin-10