Single Nucleotide Polymorphisms in the Tumor Necrosis Factor-Alpha Gene Promoter Region Alter the Risk of Psoriasis Vulgaris and Psoriatic Arthritis: A Meta-Analysis

Abstract

BackgroundIt has been confirmed that tumor necrosis factor-alpha (TNFα), a macrophage-derived pro-inflammatory cytokine, plays an important role in the pathogenesis of psoriasis vulgaris and psoriatic arthritis (PsV&PsA). In contrast, the reported association of TNFα gene promoter region single nucleotide polymorphisms (SNPs) and PsV&PsA has remained controversial. Accordingly, we performed a meta-analysis to provide new evidence that SNPs in the TNFα gene promoter region alter not only the risk of psoriasis vulgaris (PsV) or psoriatic arthritis (PsA) but also of PsV&PsA.MethodsInterrelated literature dated to October 2012 was acquired from the PubMed, ScienceDirect, and SpringerLink databases. The number of the genotypes and/or alleles for the TNFα promoter in the PsV and PsA and control subjects was obtained. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to calculate the risk of PsV and/or PsA with TNFα promoter SNPs.ResultsA total of 26 papers of 2159 for PsV (2129 normal controls) and 2360 for PsA (2997 normal controls) were included in our meta-analysis. The results showed that the variant genotype and allele of TNFα -308A/G was protective in pooled groups of patients with PsV&PsA (OR = 0.682, 0.750; 95% CI, 0.596-0.779, 0.653-0.861). However, the variant genotypes and alleles of TNFα -238A/G and -857T/C had an increased risk of PsV&PsA (OR = 2.493, 2.228, 1.536, 1.486, 95% CI, 1.777-3.498, 1.628-3.049, 1.336-1.767, 1.309-1.685). Moreover, the meta-analysis revealed a significant association between TNFα -238A/G and -857T/C polymorphism and PsA susceptibility (OR = 2.242, 2.052, 1.419, 1.465; 95% CI, 1.710-2.941, 1.614-2.610, 1.214-1.658, 1.277-1.681). In contrast, the variant genotypes and alleles of TNFα -308A/G proved to be protective against PsV (OR = 0.574, 0.650, 95% CI, 0.478-0.690, 0.556-0.759), whereas TNFα -238A/G was found to have a risk association (OR = 2.636, 2.223, 95% CI, 1.523-4.561, 1.317-3.751).ConclusionsSNPs in the TNFα gene promoter region alter the risk of PsV and/or PsA.

Tumor necrosis factor alpha gene promoter −238G/A polymorphism increases the risk of psoriasis vulgaris in Indian patients

“…The association between PsV and HLA Cw6 is relatively stronger in case of type I rather than type II psoriasis . It is not clear if the association with TNFα −238A is dependent on the disease type . In the present study, distribution of the genotype frequencies under dominant genetic model do not show any significant difference between type I and type II PsV subgroups (Table ).…”

“…A number of studies have examined the status of TNFα gene promoter sequence polymorphism in psoriasis. Data from the various reported association studies have been subjected to at least two meta‐analyses . In both the studies, the authors found that −238A allele increased the risk of psoriasis (OR = 2.6, 2.5), while −308A reduced the risk of psoriasis (OR = 0.59, 0.57).…”

TNF‐alpha gene polymorphisms can help to predict response to etanercept in psoriatic patients

“…Previous studies have evaluated a possible susceptibility role of TNF‐alpha gene polymorphisms in psoriatic arthritis but the results are conflicting. Thus, some studies have suggested a risk factor role for TNF‐alpha −238G>A and −857G>A polymorphisms, while others have failed to confirm this association . The inconsistencies in these results may reflect the small sample size of patients and controls analysed in most of the studies as well as genetic differences in the various populations.…”

“…Thus, some studies have suggested a risk factor role for TNF-alpha À238G>A and À857G>A polymorphisms, while others have failed to confirm this association. 17,18 The inconsistencies in these results may reflect the small sample size of patients and controls analysed in most of the studies as well as genetic differences in the various populations. In particular, our data might be coincidental.…”

Pharmacogenetics of Psoriasis Treatment

“…They conirmed a protective inluence of the polymorphic allele c.-308A. The polymorphic alleles of the other two frequently investigated polymorphisms also showed association with increased risk for psoriasis and PsA [42]. Another meta-analysis included nine studies with a total of 692 patients with RA.…”