Association of single nucleotide polymorphism at position ¡308 of the tumor necrosis factoralpha gene with ankylosing spondylitis and rheumatoid arthritis

Abstract

In this study, we analyzed the putative association between the ¡308 G/A polymorphism in the promoter region of the tumor necrosis factor (TNF) a gene (rs1800629) and chronic inflammatory arthritis in the Bulgarian population. A case- control study was carried out on 58 patients with ankylosing spondylitis (AS), 108 rheumatoid arthritis (RA) patients and 177 healthy subjects. ¡308 G/A TNF-a genotypes of patients and controls were determined by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). No significant association between the rs1800629 polymorphism and RA risk in the study cohort was observed. However, there were significant differences in the genotype and allele frequencies of the ¡308 G/A TNF-a polymorphism between AS patients and the healthy subjects. In logistic regression analysis, the presence of the TNF-a ¡308A allele in the genotype (AA C AG vs. GG) was associated with a 3.298 times lower risk of developing AS. In addition, in AS, there were associations for age at disease onset (<29 years; odds ratio (OR) D 0.222), disease severity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score > 4; OR D 0.152) and response to anti-TNF treatment (OR D 2.25) under a dominant model (AA C AG vs. GG). In conclusion, our results suggested that the promoter polymorphism ¡308 G/A in the TNF-a gene had no significant effect on RA development, but could play a role in AS development and in determining the age of disease onset, disease severity and therapeutic outcome of AS in the Bulgarian patients who participated in our study.