Recurrent Spontaneous Abortion (RSA) and Maternal KIR Genes: A Comprehensive Meta-Analysis

Natural killer cells (NKs) are the most important cells in the fetomaternal immune tolerance induced through interaction of maternal killer-cell immunoglobulin-like receptors (KIR) and fetal human leucocyte antigens (HLA). Hence, we intend to perform a meta-analysis on the role of maternal KIR genes diversity in recurrent spontaneous abortion (RSA). The present paper is a meta-analysis of previous genetic association studies and our previous original study. The results showed that KIR3DL1 was a significantly protecting factor for RSA (p=0.044; OR=0.833 [0.698-0.995]; fixed effect model). KIR2DS2 (p=0.034; OR=1.195 [1.013-1.408]; fixed effect model) and KIR2DS3 (p=0.013; OR=1.246 [1.047-1.483]; fixed effect model) were significantly risk factors for RSA. For KIR2DS1 there was a high heterogeneity and publication bias. Briefly, the inhibitory gene KIR3DL1 was a protecting factor, and the activating genes KIR2DS2 and KIR2DS3 were risk factors for RSA. However, the effect sizes were not suitable. We suggest further studies on different causes of pregnancy loss, to find the role of KIR2DS1.