Tumour necrosis factor alpha (TNF-α) concentration is associated with recurrent pregnancy loss (RPL). Moreover, TNF-α promoter polymorphisms affect cellular TNF-α concentrations. Although several studies on TNF-α polymorphisms have been reported, these studies only define specific loci and result in conflicting conclusions. The meta-analysis in this study was performed to examine the relationship between various TNF-α polymorphisms and RPL. We searched for articles, using MEDLINE and Embase, and performed meta-analysis of 21 studies involving 3437 cases and 4016 controls. The results demonstrated that the -308G/A polymorphism is positively associated with RPL, particularly in cases involving three or more miscarriages. For -1031T/C, -863C/A, and -376G/A polymorphisms, recessive and homozygote models revealed significant associations with RPL. However, -857C/T, -238G/A, and +488G/A polymorphisms showed no association with RPL. A subgroup analysis with respect to ethnicity demonstrated that the -308G/A and -238G/A polymorphisms are associated with RPL in Asian and Middle Eastern populations, respectively. This meta-analysis showed the associations between TNF-α polymorphisms and RPL. However, further studies of genetic polymorphisms in TNF-α other than -308G/A and -238G/A are required.
Keywords: Tumour necrosis factor alpha; meta-analysis; polymorphism; recurrent pregnancy loss.