Association of single nucleotide polymorphism at position −308 of the tumor necrosis factor-alpha 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) 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.

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

“…The found assocaitions for TNF (rs1800629) [ 19 – 22 ], TNFRSF1A (rs4149570) [ 23 ], and IL23R (rs11209026) [ 24 – 33 ] are in agreement with other case-control studies. Furthermore, Zhao et al found that the variant allele of NLRP3 (rs4612666) was associated with increased risk of AS in Chinese patients [ 23 ].…”

TNF-α gene polymorphisms and expression

“…On the other hand, in a cohort of Argentinean patients with RA, the −308A allele was neither associated with suscetibility to RA nor with the course and outcome of the disease (Aranda et al 2014 ). In addition, there was no significant association between −308 G/A polymorphism and RA risk in a cohort of Bulgarian population (Manolova et al 2014 ).…”

Polymorphisms in TNFA and IL10 gene promoters and risk of rheumatoid arthritis in Bulgarian population

“…Genotyping for the -308G/A polymorphism in the TNFA gene (rs1800629) was performed by restriction fragment length polymorphisms (RFLP) analysis of PCR fragment amplified using the modified forward primer 5-AGG CAA TAG GTT TTG AGG GCC AT 3 and the reverse primer 5-TTG GGG ACA CAC AAG CAT CAA GG 3 to create a restriction site for the NcoI enzyme as described by Manolova et al (13). Restriction enzyme of Nco1 (Thermo Scientific) digestion with the PCR product was carried out overnight at 37°C and then analyzed on a 3% agarose gel.…”