Open Access

ARTICLE

Functional study of TNF-α promoter polymorphisms: literature review and meta-analysis

Arsene Mekinian¹, Ryad Tamouza², Stephan Pavy³, Nicolas Gestermann¹, Marc Ittah¹, Xavier Mariette^1,3, Corinne Miceli-Richard^1,3

1 Université Paris XI Sud, Inserm U802, Le Kremlin-Bicêtre, France
2 Inserm U396, Immunologie et Histocompatibilité, Hôpital Saint-Louis, Paris, France
3 Service de rhumatologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

* Corresponding Author: C. Miceli-Richard,

European Cytokine Network 2011, 22(2), 88-102. https://doi.org/10.1684/ecn.2011.0285

Accepted 06 June 2011;

Abstract

The functional consequences of TNF-α promoter SNPs are still controversial and, to date, the functional consequences of TNF-α haplotype combinations in healthy subjects have not been assessed. In order to assess functional consequences of each TNF-α polymorphism and of their haplotype combination, TNF-α expression and secretion by LPS-stimulated monocytes from 50 healthy subjects were assessed. Monocytes were isolated and cultured for four hours, after 100 ng/mL LPS stimulation. mRNA expression was quantified using the real-time polymerase chain reaction, and TNF-α levels were measured by enzyme-linked immunosorbent assay. Each subject was genotyped for TNF-α -857 C/T, -238 G/A, -308 G/A polymorphisms. In order to confirm definitively the functional consequences of these TNF-α polymorphisms, we then performed a systematic review of the literature for TNF-α SNPs, and then a meta-analysis of the functional studies of the TNF-α -308 G/A SNP. No association between TNF-α mRNA or protein level expression, and TNF-α -238G/A, -308G/A, -857C/T polymorphisms, studied either independently or in haplotype combinations, was revealed. Using a meta-analysis for the TNF-α -308 G/A polymorphism, we confirmed the absence of any association between TNF-α mRNA and protein levels, and TNF-α - 308 G/A genotypes. This study and meta-analysis of the literature confirmed the absence of any functional consequences of the TNF-α -308G/A promoter polymorphism, either alone, or in various haplotype combinations in healthy subjects.

---

Keywords

---