Tumour necrosis factor-alpha gene promoter region –308 and –376 G è   a polymorphisms in Behçet's disease

J. Duymaz-Tozkir¹, A. Gül², F.A. Uyar³, U. Õzbek¹, G. Saruhan-Direskeneli³

Institute for Experimental Medical Research¹, Department of Internal Medicine, Division of Rheumatology² and Department of Physiology³, Istanbul Faculty of Medicine, Istanbul University, Turkey.

ABSTRACT
Objective
Contribution of HLA-B51 to the genetic susceptibility for Behçet's disease is well documented and recent studies suggest involvement of other genes. Tumour necrosis factor (TNF) genes are located in the vicinity of the HLA-B locus. Polymorphisms in the promoter region of TNF-a gene has been found to be associated with altered TNF secretion, and it may have a prominent role in the increased inflammatory responses of Behçet's disease. 

Methods
The study group consisted of 99 Behçet's disease patients and 96 healthy matched controls. All patients fulfilled the International Study Group criteria for Behçet's disease. The TNF-a –308 and –376 promoter alleles were assigned by the digestion of each amplified PCR product with NcoI and TasI enzymes, respectively.

Results
No significant difference was observed in the distribution of TNF-a promoter region polymorphisms be-tween patients with Behçet's disease and controls. There was no association between the presence of uncommon –308A and –376A alleles and the manifestations or severity of Behçet's disease either. The TNF-a –308A allele and HLA-B*50 was found to be associated in this series of Turkish patients and controls.

Conclusion
The role of TNF-a promoter region –308 and –376 polymorphisms in the pathogenesis of Behçet's disease is not supported by this data. The overexpression of TNF-a in Behçet's disease may be caused by other polymorphisms in the TNF gene or by post-transcriptional mechanisms.

Key words
Tumour necrosis factor, Behçet's disease, single nucleotide polymorphisms, promoter region, cytokine polymorphisms, linkage disequilibrium.

Please address correspondence to: Dr. Güher Saruhan Direskeneli, I.U.Istanbul Tip FakŸltesi Fizyoloji AD, Capa 34390, Istanbul, Turkey. 
E-mail: gsaruhan@istanbul.edu.tr

Clin Exp Rheumatol 2003; 21: (Suppl. 30): S15-S18.
© Copyright Clinical and Experimental Rheumatology 2003.