Cytokine (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies. Genes and immunity. [Genes Immun] Journal article | | Title | Cytokine (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies. | | Author(s) | Koss K, Satsangi J, Fanning GC, Welsh KI, Jewell DP | | Institution | Gastroenterology Unit, Radcliffe Infirmary, Oxford, UK. konradkoss@yahoo.com | | Source | Genes Immun 2000 Feb; 1(3):185-90. | | MeSH | Adolescent
Adult
Aged
Alleles
Case-Control Studies
Colitis, Ulcerative
Crohn Disease
Cytokines
Female
Gene Frequency
Humans
Interleukin-10
Lymphotoxin
Male
Middle Aged
Polymerase Chain Reaction
Polymorphism, Genetic
Smoking
Tumor Necrosis Factor-alpha
| | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 11196710 |
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