Polymorphism in the TNF-alpha gene promoter at position -1031 is associated with increased circulating levels of TNF-alpha, myeloperoxidase and nitrotyrosine in primary Sjögren's syndrome.
OBJECTIVE
Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine which is associated with the pathogenesis of many inflammatory diseases. The aim of this study was to investigate the effect of TNF-alpha -1031 gene polymorphism on circulating TNF-alpha, myeloperoxidase (MPO) and nitrotyrosine (NT) levels in primary Sjögren's syndrome patients.


METHODS
TNF-alpha-1031 T/C gene polymorphism was evaluated in 65 Sjögren's syndrome patients and 58 age and gender matched controls via 5' nuclease PCR analysis. Plasma TNF-alpha and NT levels were analysed by ELISA while MPO activity, total nitrate/nitrite and glutathione (GSH) levels were measured by spectral analysis.


RESULTS
TNF-alpha -1031 C carrier genotype frequency was significantly higher (p=0.045) in Sjögren patients compared to controls (23.1 vs. 10.3%, 0R= 2.83, 95% CI=0.27-7.8). Plasma TNF-alpha concentration and NT levels were also significantly higher in Sjögren patients with -1031 C carrier genotype compared to patients with TT genotype. Sjögren patients showed a significant increase in plasma MPO activity which correlated with both TNF-alpha and NT levels in subjects with -1031 C carrier genotype assessed by linear regression analysis. TNF-alpha-1031 T/C gene polymorphism had no effect on plasma nitrate/nitrite and GSH levels which were significantly decreased in Sjögren's syndrome patients compared to controls.


CONCLUSIONS
Polymorphism in the TNF-alpha gene promoter at position -1031 is associated with increased circulating levels of TNF-alpha which is correlated with increased plasma MPO activity and protein nitration in Sjögren's syndrome.
Physical Medicine-Rheumatology Clinic, Antalya Training and Research Hospital, Antalya, Turkey. drfatihcay@gmail.com
H Fatih
HF
Cay
Ilhan
I
Sezer
Serdar
S
Dogan
Rasih
R
Felek
Mutay
M
Aslan
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005978:Glutathione / Q000097:blood; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D016017:Odds Ratio; D009195:Peroxidase / Q000097:blood*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012859:Sjogren's Syndrome / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood; D015854:Up-Regulation
D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D005978:Glutathione