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).
The aim of this study was to determine whether the TNF -1031T/C (rs1799964), -376G/A (rs1800750), -308G/A (rs1800629) -238G/A (rs361525), and TNFR1 -609G/T polymorphisms are associated with RA susceptibility in a sample of Mexican patients.
This study identifies a potentially important role for TNF-α rs1800629 polymorphisms in the susceptibility to RA.However, further studies in larger cohorts are required.
A long-term observational early RA inception cohort (n = 208) with detailed information about disease activity and radiologic damage after 3, 6 and 9 years of disease was genotyped for the TNFA -308G > A promoter polymorphism (rs1800629).
In this regard, besides a strong association between the HLA-DRB1∗04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G > A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A > C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA.
In the presence of the rs1800629 AG/AA genotype, B-cell-mediated autoimmune conditions increased NHL risk (OR = 3.27, 95% CI: 2.07, 5.16; P-interaction = 0.03) in comparison with the GG genotype (OR = 1.82, 95% CI: 1.31, 2.53).
Statistically significant interactions with blood transfusion were observed for IL10RA (rs9610) (P(forinteraction) = 0.003) and TNF (rs1800629) (P(forinteraction) = 0.012) for NHL overall and IL10RA (rs9610) (P(forinteraction) = 0.001) and TNF (rs1800629) (P(forinteraction) = 0.019) for B-cell lymphoma.
TNF rs1800629 was associated with risk of NHL (OR 1.53, 95% confidence interval, CI, 1.06-2.19 for minor allele homozygosity), T-cell lymphoma (OR 2.54, CI 1.27-5.09) and mantle cell lymphoma (OR 2.84, CI 1.38-5.87).
Two single nucleotide polymorphisms (SNPs) in adjacent genes, lymphotoxin alpha (LTA +252G, rs909253 A>G) and tumor necrosis factor (TNF -308A, rs1800629 G>A), form the G-A haplotype repeatedly associated with increased risk of non-Hodgkin lymphoma (NHL) in individuals uninfected with HIV-1.
Compared with the wild-type (GG), the AA genotype for the TNF promoter polymorphism G-308A (rs1800629) was associated with increased risk of NHL [odds ratio (OR), 2.14; 95% confidence interval (95% CI), 0.94-4.85], whereas the GA genotype was not (OR, 1.00; 95% CI, 0.74-1.34).
Two common single nucleotide polymorphisms in immunoregulatory genes (TNF G308A, rs1800629 and IL10 T3575A, rs1800890) have been recently reported as risk factors for non-Hodgkin lymphoma (NHL) in a large pooled analysis.
Published data linking single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha (TNF-?) promoter region at positions -308G>A (rs1800629) and -238G>A (rs361525) to cervical cancer risk have been inconclusive.