Cytokine polymorphisms in women with recurrent pregnancy loss: Meta-analysis

Background: Inflammatory cytokine cascades have been implicated in the pathogenesis of recurrent pregnancy loss (RPL). Polymorphisms in cytokine genes may affect the risk of RPL, but genetic association studies are often limited by small sample sizes. Meta-analysis of all available studies can increase the precision of these estimates. Aims: To assess and synthesise the available data from association studies of inflammatory cytokine polymorphisms with RPL. Methods: Systematic review and random effects meta-analysis of genetic association studies. Results: Sixteen reports of genetic association studies of cytokine polymorphisms with RPL were identified. Meta-analyses did not identify any significant associations with tumour necrosis factor (-308A, or -238A), interferon-gamma (+874T), interleukin (IL)-1 beta (-511T), IL-6 (-174G), or IL-10 (-1082A, or -819T, or -592A). Significant associations were found with IL-1B (-31T) (two studies: pooled odds ratio (OR) 2.12 (95% confidence interval (CI) 1.04 to 4.33)) and IL-6 (-634G) (one study: OR 0.22 (95% CI 0.09 to 0.57)). Conclusions: The available data are not consistent with more than modest associations between these candidate cytokine polymorphisms and RPL. Data from future association studies may be added to the meta-analyses to obtain more precise estimates of effect sizes.