Polymorphisms of the 5'-Flanking Region of the Human Tumor Necrosis Factor-alpha Gene in Korean Patients with Crohn's Disease

Lee, Kil Yeon; Kim, Hyo Jong; Chi, Sung Gil; Oh, Soo Myung; Yoon, Choong; Lee, Kee Hyung

Abstract

PURPOSE: Recently, a key role of tumor necrosis factor (TNF) in the development of inflammatory bowel disease (IBD), especially Crohn's disease (CD), has emerged. In Japan, 3 single base pair polymorphisms in the 5'-flanking region of the TNF-alpha gene at position 1031, 863, and 857, which are related to high transcriptional promoter activity, have been identified in the Japanese CD patients. And the polymorphisms of the TNF-alpha gene at position 308, 238 have been reported in western CD patients. So, in order to find the same polymorphisms in Korean population and CD patients, the author evaluate the patients diagnosed with CD, ulcerative colitis (UC) and healthy controls (HCs).
METHODS
Blood samples were obtained from 70 patients with CD, 72 patients with UC and 52 healthy controls. Polymorphisms in the TNF-alpha gene at their respective positions were analyzed by single strand conformational polymorphism (SSCP), and allele frequencies in CD and UC patients were compared with those in healthy controls.
RESULTS
Allele frequencies of 1031C, 863A, and 857T in health controls were 18.3%, 8.7%, and 19.2%, respectively. Polymorphic allele frequencies of 1031C, 863A, 857T were 22.9%, 27.1%, and 24.3% in CD patients respectively. The frequencies at all 3 positions were higher in CD patients than in HCs. However, the frequency at 863A was statistically significant (P=0.000). The allele frequencies of 308A and 238A alleles were 0.7% and 3.6% in CD, 0.7% and 2.1% in UC, and 1.9% and 4.8% in HCs, respectively. The allele frequency of 1031C was significantly higher in B3 than in B2 (P=0.033).
CONCLUSION
Polymorphisms of 5'-flanking region of the TNF-alpha at positions 1031 (T/C), 863 (C/A) and 857 (C/T) may be associated with susceptibility of CD.