Association of TNF-α promoter-308 A/G polymorphism with susceptibility to systemic lupus erythematosus: a meta-analysis

Abstract

Published data on the association between tumor necrosis factor-alpha (TNF-α) promoter-308 A/G polymorphism and systemic lupus erythematosus (SLE) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 28 studies including 2,992 cases and 4,326 controls (5,924 cases and 8,484 controls in A versus G comparison) were involved in this meta-analysis. Meta-analysis was performed for genotypes A/A (recessive effect), A/A+A/G (dominant effect), and A allele in fixed or random effects models. In addition, we also performed a "model-free" analysis by considering the G/G genotype as the reference and estimated the OR for the A/A versus G/G and A/G versus G/G genotype. Overall, an association of TNF-α promoter-308 A/G polymorphism with SLE was found (A versus G: OR = 1.686, 95% CI = 1.400-2.032, P < 0.001; A/A versus A/G+G/G: OR = 3.043, 95% CI = 2.185-4.238, P < 0.001; A/A+A/G versus G/G: OR = 1.822, 95% CI = 1.379-2.407, P < 0.001; A/A versus G/G: OR = 3.686, 95% CI = 2.628-5.172, P < 0.001; A/G versus G/G: OR = 1.691, 95% CI = 1.291-2.215, P < 0.001). However, stratification by ethnicity indicated that the risk A allele was not associated with SLE in Asian (A versus G: OR = 1.207, 95% CI = 0.856-1.702, P = 0.283) and African population (A versus G: OR = 1.225, 95% CI = 0.597-2.516, P = 0.580). In summary, this meta-analysis indicated that TNF-α promoter-308-A/G polymorphism is associated with susceptibility to SLE.

Genetic Factors Contributing to Systemic Lupus Erythematosus in Tunisian Patients

“…The association of TNF-α SNPs with SLE is still not consistent. In fact, our report confirms a previous report from other authors showing an association of rs1800629 with SLE [48][49][50][51][52]. However, such association was not found in other populations [53][54][55][56][57].…”

Association of polymorphic variants of PTPN22, TNF and VDR systems in children with lupus nephritis: a study in trios of Colombian families

“…Se han hecho algunos estudios en población colombiana sobre la asociación entre el lupus eritematoso sistémico y los polimorfismos de PTPN22 (10,11), VDR (12,13) y TNF (14,15). Sin embargo, hasta la fecha solo en el estudio de Ramírez, et al (11), se había reportado la asociación del polimorfismo rs2476601, también conocido como C1858T, del gen PTPN22.…”

“…En reportes previos, se ha demostrado el papel de algunas variantes genéticas presentes en los genes PTPN22 (10,11), VDR (12,13), TNF (14,15), y HLA (16,17), entre otros (18), como factores de riesgo o de protección en los diferentes endotipos de lupus eritematoso sistémico, incluida la nefritis lúpica. La mayoría de estos estudios emplean un diseño de asociación genética de casos y controles para la detección de factores genéticos asociados a una enfermedad en particular (19,20).…”

Familial Aggregation of High Tumor Necrosis Factor Alpha Levels in Systemic Lupus Erythematosus

“…Genetic studies have implicated a promoter polymorphism in the TNF- α gene in SLE susceptibility [31], although the TNF- α gene is within the HLA locus which is characterized by multiple association signals that are difficult to resolve due to high linkage disequilibrium in the region. It is also not clear that the TNF- α promoter polymorphism functionally confers a propensity for excess TNF- α mRNA or protein production [32].…”