INFLUENCE OF POLYMORPHISM-308 G/A OF THE TNF-alpha GENE ON HIGH MOBILITY GROUP BOX-1 PROTEIN IN RHEUMATOID AND SPONDYLO-ARTHRITIS PATIENTS

作者：Bitto A; Polito F; Bagnato G; Talotta R; Atteritano M; Irrera N; Ientile R; Ferlazzo N; Caccamo D; Bagnato G; Caliri A; Squadrito F^*; Altavilla D

来源：European Journal of Inflammation, 2012, 10(3): 405-412.

DOI：10.1177/1721727X1201000316

• TNF-alpha
• SNP
• HMGB-1
• gene expression

Single nucleotide polymorphism (SNP) in the human Tumor Necrosis Factor-alpha(TNF-alpha) gene promoter, the -308 G/A variant, has been associated with increased TNF-alpha levels that may amplify the severity of rheumatoid arthritis (RA) and a poor responsiveness to TNF-alpha blockade therapy. High mobility group box protein (HMGB-1) is a pro-inflammatory cytokine that plays a pivotal role in the pathogenesis of RA and may be an original target of therapy. The aim of this study is to investigate whether the -308 C/A variant of the TNF-alpha gene is associated with altered expression of HMBG-1. A total of 110 consecutive patients with rheumatoid arthritis and spondylo-arthritis (ankylosing spondylitis, psoriatic arthritis and spondylitis associated with inflammatory bowel disease) referring to the Rheumatology Unit of Messina University Hospital were enrolled. Patients were genotyped for the -308 TNF-alpha gene promoter polymorphism. Clinical status was also assessed. HMGB-1 and TNF-alpha mRNA (Real Time PCR) from total blood and plasmatic HMGB-1 (Western Blot analysis) and TNF-alpha (ELISA) protein were also evaluated. Irrespective of the underlying disease, patients carrying the G/A genotype showed enhanced HMGB-1 and TNF-alpha mRNA levels and increased circulating concentration of the inflammatory cytokines when compared to patients with GIG genotype. The data suggest that subjects carrying the TNF-alpha -308G/A genotype have enhanced expression of HMGB-1 protein that may explain, at least in part, the increased severity of the disease.

• 出版日期2012-12