OP 55 Associations between fetal HLA-G genotype and birth and placenta weight in pregnancies complicated by preeclampsia and in uncomplicated pregnancies possible implications for HLA diversity

• Published in: Pregnancy hypertension 2017-07, Vol.9, p.34-35
• Main Authors: Emmery, Johanne, Christiansen, Ole Bjarne, Nilsson, Line Lynge, Dahl, Mette, Skovbo, Peter, Møller, Anna Margrethe, Steffensen, Rudi, F. Hviid, Thomas Vauvert
• Format: Article
• Language: English
• ISSN: 2210-7789; 2210-7797
• DOI: 10.1016/j.preghy.2017.07.076

During pregnancy, the maternal immune system must cope with the semi-allogeneic fetus in order to facilitate a successful pregnancy. The extra-villous trophoblast cells situated at the feto-maternal interface express high amounts of the immune regulatory non-classical human leukocyte antigen-G (HLA-G). A 14 base pair insertion/deletion polymorphism (14bp ins/del) in the 3″-untranslated region of the HLA-G gene has an impact on the expression level of HLA-G and a low expression of HLA-G have been linked to pregnancy complications like preeclampsia. In the present study, we investigated the impact of the fetal HLA-G 14bp ins/del genotype on the clinical outcome in normal pregnancies and pregnancies complicated by preeclampsia, in terms of birth weight and placental weight of children born by mothers heterozygous for the HLA-G 14bp ins/del. Two independent cohorts of pregnant women were used for this nested case-control study. Analysis were made on pregnancies complicated by severe preeclampsia (n=101), normal uncomplicated pregnancies (n=185) and a combination of the two. Both Taqman analyses and DNA sequencing were applied to determine the HLA-G 14bp ins/del genotype. Combining normal pregnancies and pregnancies complicated by preeclampsia and adjusting for gestational age at birth, the results show that newborns born by HLA-G 14bp heterozygous mothers that are homozygous for the HLA-G 14bp insertion, have a significantly lower birth weight (P=0.008) and lower placental weight (P=0.009) compared to newborns that are homozygous for the HLA-G 14bp deletion. The results indicate that children with the HLA-G 14bp ins/ins genotype born by mothers suffering from severe preeclampsia have a lower birthweight than children with the HLA-G 14bp ins/del or del/del genotypes born by mothers suffering from severe preeclampsia, however not significantly (P=0.08). The highest mean birth weight and placenta weight was observed in newborns homozygous for the HLA-G 14bp deletion and the lowest mean birth and placenta weight was observed in newborns homozygous for the HLA-G 14bp insertion. It can be speculated that a compromise between intermediate birth and placenta weight, HLA heterozygosity and induction of maternal tolerance have evolved in humans.