Tumour necrosis factor (-308A) polymorphism in pre-eclampsia: Meta-analysis of 16 case-control studies

The guanine to adenine transition at position -308 nucleotides in the tumour necrosis factor promoter region (TNF -308A) is a putative genetic risk factor for pre-eclampsia/eclampsia (PE/E). However, association studies have reported conflicting findings and have generally been underpowered to exclude modest effect sizes. To assess and synthesise the available evidence for the association of the TNF (-308A) polymorphism with PE/E. Systematic review and random effects meta-analysis of genetic association studies. Sixteen eligible case-control studies in which a total of 1919 patients with PE/E and 2374 controls participated were identified. The studies were generally small but of reasonable methodological quality. Random effects meta-analysis improved the precision of the estimate of effect size but did not detect a statistically significant association: pooled relative risk 1.02 (95% confidence interval 0.86 to 1.20). The available data are not consistent with more than a very modest association between the TNF (-308A) allele and PE/E. Screening pregnant women for this allele in order to guide antenatal surveillance or treatment is unwarranted. Future research efforts should focus on alternative candidate genes.