Abstract
The influence of biallelic polymorphisms in the tumour necrosis factor-alpha (TNFα), lymphotoxin-alpha (LTα) and interleukin-10 (IL-10) genes on stimulated TNFα 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 TNFα, LTα and IL-10 genes. Production of the TNFα and IL-10 was measured by ELISA in lipopolysaccharide (LPS) stimulated whole blood. Four haplotypes of the TNFα gene, three haplotypes of LTα 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-LTα-2 haplotype (56% vs 21%; P = 0.0007). The TNF-2 and LTα-2 haplotypes were associated with higher TNFα production in CD patients, and the TNF-4 haplotype was associated with lower TNFα 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 TNFα, LTα and IL-10 gene polymorphisms on cytokine production differ in CD, UC patients and controls.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Koss, K., Satsangi, J., Fanning, G. et al. Cytokine (TNFα, LTα and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies. Genes Immun 1, 185–190 (2000). https://doi.org/10.1038/sj.gene.6363657
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6363657
Keywords
This article is cited by
-
TNF-α G-308A genetic variants, serum CRP-hs concentration and DNA damage in obese women
Molecular Biology Reports (2020)
-
Immunomodulatory factors gene polymorphisms in chronic periodontitis: an overview
BMC Oral Health (2019)
-
Prosteatotic and Protective Components in a Unique Model of Fatty Liver: Gut Microbiota and Suppressed Complement System
Scientific Reports (2016)
-
Polymorphisms of tumor necrosis factor alpha in Middle Eastern population with colorectal cancer
Tumor Biology (2016)
-
Cytokine Gene Considerations in Giant Cell Arteritis: IL10 Promoter Polymorphisms and a Review of the Literature
Clinical Reviews in Allergy & Immunology (2014)