The purpose of this work was to analyze the possible influence of TNF loci polymorphism on the susceptibility and/or the disease profile of rheumatoid arthritis (RA). Tumor necrosis factor (alpha and beta) genotypes were determined in 60 patients with RA and 102 healthy subjects by a method based on PCR-RFLP with amplification-created restriction sites. The results obtained in the present study showed that there is not a significant association of either TNF alpha promoter variation (at positions -308 and -238) or TNF beta polymorphism with susceptibility to RA. However, a significant difference in the mean age at disease onset was found between -238 TNF alpha genotypes. In addition, a difference in the presence of nodular disease was observed between -308 TNF alpha genotype. The results of this study suggests that the TNF alpha gene may play a role in the disease profile of rheumatoid arthritis.

These results indicate that the FcgammaRIIIA-158 genotypes confer differential susceptibility to RA in our study population. Further studies to elucidate the role of this polymorphism in the pathogenesis of RA and other autoimmune diseases are warranted.

No abstract

Interleukin-18 (IL-18), a member of the IL-1 family, is known to play a relevant role in rheumatoid arthritis (RA) physiopathology mainly by promoting the inflammatory response. The aim of this work was to investigate the possible implication of two single-nucleotide polymorphisms (SNPs) [-607 A/C (rs1946518) and -137 G/C (rs187238)] within the IL-18-promoter region in RA predisposition and clinical course. A total of 362 unrelated RA patients and 339 healthy controls were genotyped using a real-time polymerase chain reaction (PCR) method for the -607 A/C SNP and a sequence-specific PCR method (PCR-SSP) for the -137 G/C polymorphism. No statistically significant differences were observed for both -607 and -137 IL-18-promoter polymorphisms between RA patients and controls, considering either allelic or genotypic frequencies. In addition, no association was found with the haplotypes inferred by the two polymorphisms and RA susceptibility. This was also the case when RA patients were stratified according to sex, age at the onset of the disease, rheumatoid factor status, and extraarticular manifestations. Our data suggest that -607 A/C (rs1946518) and -137 G/C (rs187238) polymorphisms within the IL-18-promoter region do not play a major role in RA predisposition.

Objective-The aim of this study was to investigate the relation between the polymorphism of large molecular weight proteasome (LMP) (LMP2-LMP7) and transporter associated with antigen processing (TAP) (TAP1-TAP2) genes and rheumatoid arthritis (RA). Methods-Sixty RA patients and 102 ethnically matched unrelated healthy subjects were typed for LMP, TAP, and disease associated HLA-DRB1 alleles by using a new strategy based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with amplification created restriction sites. Results-The polymorphism of LMP (LMP2-LMP7) and TAP (TAP1-TAP2) genes was examined in shared epitope positive and negative RA patients and controls. No significant diVerences in the LMP or TAP allele frequencies were observed between the total patient and control groups or the patients and controls positive or negative for the shared epitope. Conclusion-The data suggest that the polymorphisms of LMP and TAP genes do not have an important influence in the pathogenesis of RA, although larger studies will be needed to provide more conclusive evidence on the role of these genes in RA. A new, highly reliable strategy for typing LMP alleles is also described.