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

이명수|이은경|김상욱|채수진|전창덕|염주진|최석제|이성가|서점성
대한면역학회 (The Korean Association of Immunologists)|2005.12|Immune Network|제5권 제4호|pp. 205-214

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초록

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.

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