Abstract
Although a number of studies reported the association of HLA-DRB1 and Crohn’s disease (CD), the actual alleles associated with CD are considerably variable among populations. On the other hand, the relevance of tumor necrosis factor α (TNFα) in the pathogenesis of CD is established through experimental as well as clinical studies, raising the possibility that TNFA polymorphism is primarily or independently contribute to the association of HLA region genes with CD. New polymorphisms which may affect the transcriptional activity were recently reported within the upstream promoter region of TNFA gene. In the present study, we compared HLA-DRB1, TNFA promoter and TNF receptor 2 (TNFR2) genotypes in 154 Japanese patients with CD and 265 unrelated healthy controls to evaluate the individual contribution of these genes to the genetic predisposition to CD. Significant positive association was observed in HLA-DRB1*0405 (P = 0.001, odds ratio (OR) = 2.02) and 0410 (P = 0.002, OR = 4.79). Among the TNFA promoter haplotypes, TNFA-U03 (−1031C, −863A, −857C) was significantly increased (P = 0.008, OR = 1.64), while TNFA-U04 (−1031C, −863C, −857C) was significantly decreased (P = 0.014, OR = 0.12), in CD. The association with TNFA-U03 was independent of that with DRB1*0405 and 0410, and apparent additive or multiplicative effect was not observed between these susceptibility alleles. No association was observed between TNFR2–196M/R polymorphism and CD. These results indicated that both of HLA-DRB1 and TNFA promoter polymorphisms contribute to the susceptibility to CD in an independent manner.
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
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
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
Additional information
This study was supported by the Grant-in-Aid for Scientific Research (B) (11470505) and Grant-in-Aid for Exploratory Research (C) (10877087) from the Ministry of Education, Science, Sports and Culture.
Rights and permissions
About this article
Cite this article
Kawasaki, A., Tsuchiya, N., Hagiwara, K. et al. Independent contribution of HLA-DRB1 and TNFα promoter polymorphisms to the susceptibility to Crohn’s disease. Genes Immun 1, 351–357 (2000). https://doi.org/10.1038/sj.gene.6363689
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6363689
Keywords
This article is cited by
-
Intestinal mucosa-derived DNA methylation signatures in the penetrating intestinal mucosal lesions of Crohn’s disease
Scientific Reports (2021)
-
Associations of HLA class I alleles in Japanese patients with Crohn’s disease
Genes & Immunity (2015)
-
A meta-analysis on the association between three promoter variants of TNF-α and Crohn’s disease
Molecular Biology Reports (2012)
-
Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection
Journal of Genetics (2007)
-
Susceptibility to JRA/JIA: complementing general autoimmune and arthritis traits
Genes & Immunity (2006)