J Korean Med Sci.  2006 Aug;21(4):596-601. 10.3346/jkms.2006.21.4.596.

Association of TNFA Promoter Region Haplotype in Behcet's Disease

• Park KS
• Kim NY
• Nam JH
• Bang D
• Lee ES

• KMID: 2157807
• DOI: http://doi.org/10.3346/jkms.2006.21.4.596

Abstract

Although the etiology of Behcet's Disease (BD; MIM 109650) remains to be clearly elucidated, levels of tumor necrosis factor alpha (TNF-alpha) have been reported to be significantly elevated in BD patients, and TNF-alpha blockers have been demonstrated to exhibit some degree of therapeutic efficacy for a certain subset of BD sufferers. In this study, we have conducted an analysis of the TNFA haplotypes in the promoter response element that affect the binding affinity of specific transcription factors, in order to characterize their association with the clinical features of BD. Six polymorphisms in the promoter region of TNFA were genotyped in 254 BD patients and 344 control subjects, via the PCR-RFLP technique. TNFA -1031*C, -863*A and -308*G alleles were associated with an increased risk of BD (p=0.030, OR=1.4; p=0.008, OR=1.5; p=0.010, OR=1.8, respectively). The sole TNFA haplotype -1031C-863A-857C-376G-308G-238G, was associated with a 1.6 fold increase in the risk of BD, whereas the TNFA haplotype -1031T-863C-857C-376G-308A-238G was associated with a 0.6 decreased risk of BD. The TNFA -1031*C, -863*A, -857*C and -308*G alleles were significantly associated with BD. The findings of this study, collectively, indicate that TNFA haplotypes in the promoter response elements may exert significant influence on susceptibility to BD.

Keyword

Tumor Necrosis Factor-alpha; Behcet Syndrome; Haplotypes; Polymorphisms, Single Nucleotide

MeSH Terms

Tumor Necrosis Factor-alpha/*genetics
Promoter Regions (Genetics)/*genetics
Polymorphism, Single Nucleotide/genetics
Odds Ratio
Middle Aged
Male
Linkage Disequilibrium
Humans
Haplotypes/*genetics
Genotype
Genetic Predisposition to Disease/genetics
Gene Frequency
Female
Behcet Syndrome/*genetics/pathology
Aged
Adult
Adolescent

Figure

• 

  Fig. 1 Allele frequency of the TNFA promoter in BD onset age.

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