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

Hocher, Bertholda; Chen, You-Penga e; Schlemm, Ludwiga; Burdack, Alinea; Li, Jiana e; Halle, Horstb; Pfab, Thiemoa c; Kalk, Philippa c; Lang, Floriand; Godes, Michaela

doi: 10.1097/FPC.0b013e328330bc7a
ORIGINAL ARTICLES
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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 Charité 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.

aCenter for Cardiovascular Research/Institute of Pharmacology

bDepartment of Obstetrics and Gynecology

cDepartment of Internal Medicine IV/Nephrology (UKBF), Charité, Berlin

dInstitute of Physiology, University of Tübingen, Tübingen, Germany

eDepartment of Infectious Diseases, the first Affiliated Hospital of Jinan University, Guangzhou, China

Correspondence to Professor Berthold Hocher, Center for Cardiovascular Research/Institute of Pharmacology, Charité Mitte, Hessische Street 3-4, Berlin 10115, Germany

Tel: +49 30 450 514098; fax: +49 30 450 514938;

e-mail: berthold.hocher@charite.de

Received 17 May 2009 Accepted 11 July 2009

© 2009 Lippincott Williams & Wilkins, Inc.