Abstract
Celiac disease (CD) remains one of the most significant autoimmune diseases worldwide. The pathogenesis of CD is not clearly understood and is probably attributed to genomic variations and host genetic make-up. Case-control and cohort studies of the association between the TNF-α -308 G > A (rs1800629) polymorphism and CD susceptibility have yielded inconsistent results. In this study, PubMed, EMBASE, and Google Scholar web-databases were searched for pertinent reports showing association of TNF-α -308 G > A gene with CD risk. A total of eleven reports involving 1774 controls and 1147 CD cases were included. Significant associations in four genetic models, viz. variant allele (A vs. G: p = 0.001; OR = 2.051, 95% CI = 1.452–2.895), variant homozygous (AA vs. GG: p = 0.001; OR = 6.626, 95% CI = 3.569–12.300), recessive (AA vs. GG + AG: p = 0.001; OR = 4.766, 95% CI = 3.177–7.152) and dominant (AA + AG vs. GG: p = 0.008; OR = 1.910, 95% CI = 1.181–3.088) were found in comparison with wild type homozygous GG genotype. However, heterozygous genetic model did not show any association. Sensitivity analysis revealed stable and statistically robust results. Our results suggest that TNF-α -308 G > A gene polymorphism significantly contributes to CD susceptibility.
Highlights
Single nucleotide polymorphisms (SNPs) have been noted in the TNF-α gene[11]
Most of the evidences suggest that the endogenous production of TNF-αmay be influenced by TNF-αpromoter polymorphisms, thereby affecting messenger RNA and protein expression levels[26]
Our meta-analysis showed that odds ratios (ORs) of the four genetic models were on the right side of the vertical line and the corresponding 95% confidence intervals (CIs) of the pooled ORs were on the right side of the vertical line with a significant p-value
Summary
Among them one G (guanine) >A (adenine) polymorphism is located upstream of the gene at -308 and is known to influence TNF-αlevels. The location of the gene within the major histocompatibility complex and the putative role of -308 G >A polymorphism on the promoter activity of TNF-α gene has raised the possibility that this polymorphism may influence immunologic homeostasis and contribute to the pathogenesis of CD. Keeping aforesaid information in view, to date a number of case control and cohort studies have been performed to investigate the association of TNF-α -308 G >A gene polymorphism and CD susceptibility[14,15,16,17,18,19,20,21,22,23,24]. The schematic representation of the entire pooled study is presented as Graphical Abstract (Fig. 1)
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