Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis

Abstract

Tumor necrosis factor-alpha ( TNF-α ) plays an important role in autoimmune diseases. Previous studies have investigated the association of TNF-α-238G/A (rs361525) and -308G/A (rs1800629) polymorphisms with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, no agreed conclusion had been made. Therefore, this meta-analysis was conducted to assess the associations of TNF-α-238G/A and -308G/A polymorphisms with RA and SLE risk. A systematic search was conducted in commonly used databases. Meta-analysis was performed by STATA12.0. A total of 43 studies were included. In the overall population, the TNF-α-238A allele was observed to be a protective factor for RA (A vs G: OR=0.75, 95%CI=0.57–0.99, P=0.040) and the TNF-α-308A allele was found to be a risk factor for SLE (A vs G: OR=1.78, 95%CI=1.45–2.19, P<0.001). However, no evidence of association was found between TNF-α -238 G/A polymorphism and SLE nor between -308G/A and RA. In the subgroup analysis, TNF-α-308A allele played a pathogenic role for RA in Latin Americans (A vs G: OR=1.46, 95%CI=1.15–1.84, P=0.002) and for SLE in Latin Americans (A vs G: OR=2.12, 95%CI=1.32–3.41, P=0.002) and Europeans (A vs G: OR=2.03, 95%CI=1.56–2.63, P<0.001), while it played a protective role for RA in Asians (A vs G: OR=0.54, 95%CI=0.32–0.90, P=0.017). No significant association was found between TNF-α-308G/A and SLE susceptibility in Africans and Asians. This meta-analysis demonstrated that TNF-α-238A was associated with decreased risk of RA rather than SLE, while -308G/A polymorphism was associated with SLE rather than RA. Stratification analysis indicated that different ethnicities would have different risk alleles.

Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset

“…A SNP in IRF5, rs3807306, is another common autoimmune susceptibility locus associated with RA, SLE, MS, and Crohn's disease (CD) and is linked to higher serum interferon-α (IFNα) activity (measured by a reporter cell line) in SLE (7,(16)(17)(18). The SNP rs1800629 in TNF is linked to various autoimmune diseases, including CD, celiac disease, RA, and SLE (6,(19)(20)(21). Another SNP in the TNF gene rs1799724 is associated with CD and autoimmune hepatitis (AIH) (22,23).…”

The associations of TNF‐α gene polymorphisms with bone mineral density and risk of osteoporosis: A meta‐analysis

“…Furthermore, it is also well acknowledged as a proinflammatory cytokine that promotes the development of various autoimmune diseases such as gout, osteomyelitis and RA, most of which were accompanied by osteoporosis . For instance, previous studies indicated that the release of TNF‐α might cause bone loss in the joints and throughout the skeleton in RA patients . Additionally, the bone loss in gout and osteomyelitis patients was also observed to be associated with TNF‐α levels .…”

“…23 For instance, previous studies indicated that the release of TNF-α might cause bone loss in the joints and throughout the skeleton in RA patients. [24][25][26] Additionally, the bone loss in gout and osteomyelitis patients was also observed to be associated with TNF-α levels. 27,28 Therefore, TNF-α may be an important pro-osteoclastic factor associated with osteoporosis of various etiologies.…”

Tumor necrosis factor‑α in systemic lupus erythematosus: Structure, function and therapeutic implications (Review)

“…TNF-α is involved in the pathogenesis of numerous autoimmune disorders, such as rheumatoid arthritis (RA) (3), inflammatory bowel disease (4,5), psoriatic arthritis (6) and multiple sclerosis (7,8); however, its role in systemic lupus erythematosus (SLE) disease remains unclear. From the genetic point of view, several investigations have demonstrated a link between the TNF-α gene polymorphism and the susceptibility to SLE (9)(10)(11). Furthermore, there is a strong connection between TNF-α gene expression and clinical manifestations in patients with SLE (12).…”