Dataset Information

Tumor necrosis factor-α gene promoter -308 and -238 polymorphisms and its serum level in psoriasis.

ABSTRACT:

Background

Psoriasis is a chronic, immune-mediated, inflammatory skin disease affecting genetically predisposed individuals and requiring long-term treatment. The etiology of psoriasis is not fully understood. This article aimed to determine association between genetic polymorphisms in tumor necrosis factor-α (TNF -α) promoter -308 (rs1800629) and -238 (rs 361,525) and its serum level in psoriasis patients.

Methods

The study was conducted on 70 patients with psoriasis and 70 age and sex-matched, healthy individuals. All patients were subjected to history taking and complete medical examination. The polymorphisms of TNF -α promoter gene -308 (rs1800629) and -238 (rs 361,525) were detected by real time PCR and Serum levels of TNF -α were measured by ELISA technique.

Results

AG polymorphism and A allele of TNF-α -238 G/A (rs 361,525) were significantly more in patients than controls, whereas AG polymorphism and A allele of TNF-α -308 G/A (rs1800629) were significantly more in controls than patients. There were significant high levels of TNF-α in serum of patients in comparison to controls.

Conclusions

The AG polymorphism and A allele of TNF-α -238G/A (rs 361,525) may act as a risk factor for occurrence of psoriasis, whereas AG polymorphism and A allele of TNF-α -308G/A (rs1800629) may have protective role. There is pivotal role of TNF-α as a pro-inflammatory mediator in pathogenesis of psoriasis.

SUBMITTER: Hagag MM

PROVIDER: S-EPMC8209664 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Individual studies have assessed the association between TNF-α-308G>A and TNF-α-238 G>A polymorphisms and severity of dengue infection. However, the results are inconclusive and most studies had small sample sizes. The objective of this study was to summarize the evidence of association between TNF-α-308 G>A and TNF-α-238 G>A and severity of dengue infection. This study follows the preferred reporting items for systematic reviews and meta- analyses of genetic association studies, recommended by PLOS One. We calculated pooled odds ratio and its 95% confidence interval (CI) to estimate the association between TNF-α-308 G>A or TNF-α-238 G>A and the risk of severe dengue infections. To determine the information size required for this meta-analysis study, a trial sequential analysis (TSA) was done. Eight studies (640 cases and 1275 controls), which assessed the association of TNF-α-308 G>A or TNF-α-238 G>A and the risk of DHF were included. Overall, we found no significant association between TNF-α-308 G>A and the DHF risk in the allelic model (OR, 0.91; 95% CI, 0.51-1.63), the recessive model (OR,1.32;95%CI,0.73-2.37), the dominant model (OR,0.93;95%CI:0.59-1.47) or the additive model (OR,1.43,95;95%CI:0.79-2.59). There was also no significant association between TNF-α-238 G>A and DHF risk under the allele contrast model (OR:1.51;95%CI:0.88-2.58), the recessive model (OR,1.48,95% CI:0.33-6.58), the dominant model (OR,1.48;95%CI:0.56-3.92), or the additive model (OR:1.5;95%CI:0.34-6.69). On subgroup analysis, neither the Asian population nor the non-Asian population showed significant association between TNF-α-308 G>A/TNF-α-238 G>A and the DHF risk under any genetic models. Leave-one-out meta-analysis showed stability of the results. TSA plots suggested that the sample size in this meta-analysis study was below the required information size. The findings suggest an inclusive evidence of the association between TNF-α-308/ TNF-α-238 G>A and the risk of developing severe dengue infection. Large studies with evidence of Hardy-Weinberg equilibrium, assessing gene-gene interactions are recommended.

Project description:BackgroundTumor necrosis factor-α (TNF-α) may play an important role in the recalcitrant inflammatory and hyperproliferative dermatosis of psoriasis, and there may be a relationship between TNF-α polymorphisms and psoriasis risk.MethodsWe performed a meta-analysis to evaluate the associations between TNF-α polymorphisms and psoriasis. Electronic searches of Pubmed, Embase, and Web of Science were performed for all publications on the associations between TNF-α polymorphisms and psoriasis through September 26, 2012. The pooled odds ratios (ORs) with their 95% confidence interval (95%CIs) were calculated to assess the associations.ResultsSixteen case-control studies with a total of 2,253 psoriasis cases and 1,947 controls on TNF-α 308 G/A polymorphism and fourteen studies on TNF-α 238 G/A polymorphism with 2,104 cases and 1,838 controls were finally included into the meta-analysis. Overall, TNF-α 308 G/A polymorphism was significantly associated with decreased risk of psoriasis under three genetic comparison models (for A versus G: fixed-effects OR 0.71, 95%CI 0.62-0.82, P < 0.001; for AG versus GG: fixed-effects OR 0.67, 95%CI 0.57-0.78, P < 0.001; for AA/AG versus GG: fixed-effects OR 0.67, 95%CI 0.58-0.78, P < 0.001). In addition, TNF-α 238 G/A polymorphism was associated with increased risk of psoriasis under three genetic models (for A versus G: fixed-effects OR 2.46, 95%CI 2.04-2.96, P < 0.001; for AG versus GG: fixed-effects OR 2.69, 95%CI 2.20-3.28, P < 0.001; for AA/AG versus GG: fixed-effects OR 2.68, 95%CI 2.20-3.26, P < 0.001). Subgroup analysis by ethnicity identified a significant association between TNF-α 308 G/A polymorphism and decreased risk of psoriasis in both Caucasians and Asians and a significant association between TNF-α 238 G/A polymorphism and increased risk of psoriasis in Caucasians.ConclusionsThe meta-analysis suggests that TNF-α 308 G/A polymorphism is associated with decreased risk of psoriasis, while TNF-α 238 G/A is associated with increased risk of psoriasis.