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.

Abstract

OBJECTIVES: 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.