High expression of TNF alpha is associated with-308 and-238 TNF alpha polymorphisms in knee osteoarthritis

Knee osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage components due to an imbalance between extracellular matrix destruction and repair. The proinflammatory cytokines involved in OA, TNF alpha and IL1 beta, are considered the major implicated. The aim of this study was to investigate the relationship between TNF alpha -308 and -238 polymorphisms with messenger RNA (mRNA) and soluble TNF alpha expression in knee OA patients and healthy subjects (HS). Case-control study involved 50 knee OA patients classified according to 1986 ACR Classification Criteria, as well as 100 HS. The Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne disability index were applied to OA patients. The -308 and -238 polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism technique. The TNF alpha mRNA expression was quantified by real-time PCR using TaqMan method. The sTNF alpha levels were measured by enzyme-linked immunosorbent assay. The TNF alpha mRNA expression in knee OA patients was higher than in HS (1.56-fold). In addition, the TNF alpha mRNA expression was higher in carriers of G allele in the knee OA group for both polymorphisms. The sTNF alpha levels were increased in G/G versus G/A genotypes in both studied polymorphisms (p < 0.05). However, the TNF alpha -308 and -238 genotypes did not show statistical differences between groups. The G allele of TNF alpha -308 and -238 polymorphisms is associated with high mRNA and soluble expression in knee OA patients. However, it is not a marker of susceptibility in Western Mexico. Further studies are necessary to confirm these findings.