Fetal sex determines the impact of maternal PROGINS progesterone receptor polymorphism on maternal physiology during pregnancy

Background Recent evidence from very rare human diseases suggests that variation in the fetal genome can modify maternal physiology during pregnancy. Here, we tested the hypothesis that fetal sex as a major genetic variant of the fetal genome may affect maternal physiology during pregnancy in genetically susceptible pregnant women. Methods We analyzed the impact of fetal sex on maternal physiology during pregnancy in relationship with the maternal PROGINS progesterone receptor gene polymorphism. Two thousand and eighty-nine (2089) Caucasian women without preexisting diabetes and preexisting hypertension with singleton pregnancies delivering consecutively at the Charite obstetrics department participated in this study. Results The maternal PROGINS progesterone receptor polymorphism on its own had no effect on blood pressure, new onset of proteinuria, and total glycated hemoglobin at delivery. However, by considering the offspring's sex, the AA variant of the PROGINS progesterone receptor polymorphism was associated with profound cardiovascular/metabolic effects; mothers carrying both A alleles (AA genotype) delivering a boy had significantly lower systolic blood pressure during the first trimester of pregnancy versus AA mothers delivering girls (107.9 +/- 10.2 vs. 116.6 +/- 15.1 mmHg, P=0.044). Diastolic blood pressure was similarly lower during the first trimester of pregnant AA women delivering boys in comparison with AA women delivering girls (63.4 +/- 5.7 vs. 68.2 +/- 10.9 mmHg, P=0.032). Total glycated hemoglobin at delivery was significantly (P=0.002) higher in AA mothers delivering boys (6.6 +/- 0.7%) versus AA mothers delivering girls (5.9 +/- 0.6%). Conclusion Our study indicates that fetal sex may substantially affect maternal blood pressure as well as glycemic control during pregnancy in genetically susceptible mothers. Pharmacogenetics and Genomics 19:710-718 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.