Tumour necrosis factor-alpha gene promoter region -308 and -376 G-->A polymorphisms in Behçet's disease.
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-alpha 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-alpha -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-alpha promoter region polymorphisms between 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-alpha -308A allele and HLA-B*50 was found to be associated in this series of Turkish patients and controls.


CONCLUSIONS
The role of TNF-alpha promoter region -308 and -376 polymorphisms in the pathogenesis of Behçet's disease is not supported by this data. The overexpression of TNF-alpha in Behçet's disease may be caused by other polymorphisms in the TNF gene or by post-transcriptional mechanisms.
Duymaz-Tozkir
J
J
Institute for Experimental Medical Research, Istanbul Faculty of Medicine, Istanbul University, Turkey.
Gül
A
A
Uyar
F A
FA
Ozbek
U
U
Saruhan-Direskeneli
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D001528:Behcet Syndrome / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics; D059949:HLA-B51 Antigen; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011336:Probability; D011401:Promoter Regions, Genetic; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015235:HLA-B Antigens; D059949:HLA-B51 Antigen; D014409:Tumor Necrosis Factor-alpha