Immune Netw.  2005 Dec;5(4):205-214. 10.4110/in.2005.5.4.205.

Ulcerative Colitis is Associated with Novel Polymorphisms in the Promoter Region of MIP-3alpha/CCL20 Gene

Affiliations
  • 1Digestive Disease Research Institute, Korea.
  • 2Genome Research Center for Immune Disorders, Wonkwang University School of Medicine, Iksan, Korea.
  • 3Department of Physiology, Kyungpook National University School of Medicine, Daegu, Korea. cdjun@knu.ac.kr
  • 4Department of Internal Medicine, Chonbuk National University College of Medicine, Jeonju, Korea.

Abstract

BACKGROUND
We examined global gene expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with ulcerative colitis (UC), and tested whether the identified genes with the altered expression might be associated with susceptibility to UC. METHODS: PBMCs from 8 UC and 8 normal healthy (NH) volunteers were collected, and total RNAs were subjected to the human 8.0K cDNA chip for the microarray analysis. Real time-PCR (RT-PCR) was performed to verify the results of microarray. One hundred forty UC patients and 300 NH controls were recruited for single nucleotide polymorphism (SNP) analysis. RESULTS: Twenty-five immune function-related genes with over 2-fold expression were identified. Of these genes, two chemokines, namely, CXCL1 and CCL20, were selected because of their potential importance in the evocation of host innate and adaptive immunity. Four SNPs were identified in the promoter and coding regions of CXCL1, while there was no significant difference between all patients with UC and controls in their polymorphisms, except minor association at g.57A< G (rs2071425, p=0.02). On the other hand, among three novel and one known SNPs identified in the promoter region of CCL20, g.-1,706 G< A (p=0.000000055), g.-1,458 G< A (p=0.0048), and g.-962C< A (p=0.0006) were found to be significantly associated with the susceptibility of UC. CONCLUSION: Altered gene expression in mononuclear cells may contribute to IBD pathogenesis. Although the findings need to be confirmed in other populations with larger numbers of patients, the current results demonstrated that polymorphisms in the promoter region of CCL20 are positively associated with the development of UC.

Keyword

Inflammatory bowel diseases; ulcerative colitis; crohn's disease; single nucleotide polymorphism

MeSH Terms

Adaptive Immunity
Chemokines
Clinical Coding
Colitis, Ulcerative*
Crohn Disease
DNA, Complementary
Gene Expression
Hand
Humans
Inflammatory Bowel Diseases
Microarray Analysis
Polymorphism, Single Nucleotide
Promoter Regions, Genetic*
RNA
Transcriptome
Ulcer*
Volunteers
Chemokines
DNA, Complementary
RNA
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