Analysis of association between maternal tumor necrosis factor-alpha promoter polymorphism (-308), tumor necrosis factor concentration, and preterm birth.
OBJECTIVE
This study was undertaken to investigate the association of tumor necrosis factor-alpha (TNF-alpha) 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-alpha concentration in amniotic fluid (AF) in preterm birth was also investigated.


METHODS
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-alpha 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-alpha concentration was demonstrated with the GG genotype in cases compared with the presence of allele A.


CONCLUSIONS
Meta-analysis of available evidence documented no statistically significant association between a single nucleotide polymorphism in the TNF-alpha gene (G-308>A) and preterm birth. Analyses of AF-TNF-alpha concentration demonstrated no increase in TNF-alpha in the presence of the minor allele (A). These results suggest that this single nucleotide polymorphism does not independently associate strongly with preterm birth.
Menon
Ramkumar
R
The Perinatal Research Center, Nashville, TN 37203, USA.
Merialdi
Mario
M
Betrán
Ana P
AP
Dolan
Siobhan
S
Jiang
Lan
L
Fortunato
Stephen J
SJ
Williams
Scott
S
D000225:Adenine; D000653:Amniotic Fluid / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006147:Guanine; D006801:Humans; D009994:Osmolar Concentration; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy / Q000235:genetics* / Q000378:metabolism; D047928:Premature Birth / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D000225:Adenine