Association of single nucleotide polymorphism at position -308 of the tumor necrosis factor-alpha gene with ankylosing spondylitis and rheumatoid arthritis

In this study, we analyzed the putative association between the -308 G/A polymorphism in the promoter region of the tumor necrosis factor (TNF) α 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-α 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-α polymorphism between AS patients and the healthy subjects. In logistic regression analysis, the presence of the TNF-α -308A allele in the genotype (AA + 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) = 0.222), disease severity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score > 4; OR = 0.152) and response to anti-TNF treatment (OR = 2.25) under a dominant model (AA + AG vs. GG). In conclusion, our results suggested that the promoter polymorphism -308 G/A in the TNF-α 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.