Analysis of association between maternal tumor necrosis factor-α promoter polymorphism (-308), tumor necrosis factor concentration, and preterm birth

Objective: This study was undertaken to investigate the association of tumor necrosis factor-α (TNF-α) single nucleotide polymorphism (G-308>A) and risk of preterm birth by performing a systematic review and a meta-analysis of available studies. In addition, association between this variant and TNF-α concentration in amniotic fluid (AF) in preterm birth was also investigated. Study design: Articles were chosen based on a Medline and EMBASE searches (1990-2005) with no language restrictions. An ongoing case-control study conducted in Nashville, TN, was also included. Articles evaluating the association between G-308>A and preterm birth were screened according to specific inclusion criteria. Meta-analysis was performed by using a random effect model. Association between maternal -308 genotype and AF-TNF-α concentration was determined by sandwich immunoassays. Results: Titles and abstracts of 6851 citations identified through the search were screened. Including our own study, a total of 7 studies were included for meta-analysis. Only 2 reported a statistically significant increased risk based on -308 genotype. Meta-analysis of the case-control studies on a pooled dataset (a total of 1846 subjects, 638 cases, and 1208 controls) showed no significant association between the -308 genotype and the risk of preterm birth (odds ratio [OR] 1.41; CI 0.90-2.19). A nonsignificant increase of AF TNF-α concentration was demonstrated with the GG genotype in cases compared with the presence of allele A. Conclusion: Meta-analysis of available evidence documented no statistically significant association between a single nucleotide polymorphism in the TNF-α gene (G-308>A) and preterm birth. Analyses of AF-TNF-α concentration demonstrated no increase in TNF-α in the presence of the minor allele (A).These results suggest that this single nucleotide polymorphism does not independently associate strongly with preterm birth.