Meta‐analysis of the human leukocyte antigen‐G ( HLA ‐G) 14 bp insertion/deletion polymorphism as a risk factor for preeclampsia

The non‐classical major histocompatibility complex, human leukocyte antigen ( HLA )‐G, plays an important role in pregnancy. HLA ‐G mediates proper interaction between maternal immune cells and fetal trophoblasts invading the uterine wall, to ensure successful placental development and function. Several HLA ‐G gene variants have been shown to be associated with development of preeclampsia ( PE ), but the reported associations of the HLA ‐G 14 base pair (bp) insertion/deletion (I/D) polymorphism (rs66554220) with PE are inconsistent. In this meta‐analysis of HLA ‐G 14 bp I/D in each member of the family triad, we estimated risk (odds ratio [ OR ], 95% confidence interval) of associations with PE based on nine published offspring, nine mother and three father case–control studies. No significant increased risk associations between PE and HLA ‐G 14 bp I/D were detected in any of the family triad members (offspring: OR = 1.08–1.21, P = 0.57–0.74; mothers: OR = 1.11–1.28, P = 0.07–0.44; fathers: OR = 1.09–1.65, P = 0.07–0.70). Of the 20 comparisons performed, 14 (70%) were non‐heterogeneous and seven of these had zero heterogeneity ( I 2 = 0%). Sensitivity treatment confirmed robustness for the overall lack of association for HLA ‐G 14 bp I/D. In subgroup analysis, significant association between HLA ‐G 14 bp I/D and PE was shown in offspring from primipara ( OR = 1.66–1.95, P = 0.04) and European Caucasian pregnancies ( OR = 1.37–2.03, P = 0.02–0.03). However, heterogeneity and sensitivity tests suggest that further investigation is needed to determine if HLA ‐G 14 bp I/D is involved in trophoblast HLA ‐G expression and PE development in these subgroups.