[show abstract][hide abstract] ABSTRACT: HYPOTHESIS/ INTRODUCTION: : We recently demonstrated that fetal sex may affect maternal glycaemic control in genetically prone mothers. We tested the hypothesis that fetal sex/fetal Y/X chromosomes might affect maternal glycaemic control during pregnancy depending on the maternal angiotensin converting enzyme (ACE) I/D polymorphism.
: One thousand, three hundred and thirty-two Caucasian women without pre-existing diabetes and pre-existing hypertension with singleton pregnancies delivering consecutively at the Charité obstetrics department were genotyped. Glycaemic control was analysed by measuring total glycated haemoglobin at birth. Correction for confounding factors and multiple testing was done.
: Maternal ACE I/D polymorphism showed significant interaction with fetal sex concerning maternal total glycated haemoglobin. Total glycated haemoglobin in DD mothers delivering boys was 6.42 ± 0.70% vs. 6.21 ± 0.66% in DD mother delivering girls (p < 0.005), whereas the II carrying mothers showed the opposite effect. II mothers delivering a girl had a higher (p = 0.044) total glycated haemoglobin at birth (6.40 ± 0.80%) compared to II mothers delivering boys (6.21 ± 0.81%). There was no interaction of the ACE I/D polymorphism and fetal sex with respect to new onset proteinuria, new onset edema and pregnancy-induced hypertension.
: Maternal glycaemic control during the last weeks of pregnancy seems to be influenced by an interaction of the ACE I/D genotyp and fetal sex.
Journal of Renin-Angiotensin-Aldosterone System 03/2011; 12(3):254-61. · 2.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Low birth weight is associated with an increased risk of cardiovascular events in later life. Insulin resistance is a key finding in adult patients with cardiovascular diseases. The neonatal phenotype of an individual with insulin resistance might be low birth weight, as insulin influences fetal growth. The renin-angiotensin-aldosterone system has been associated with cardiovascular disease and insulin resistance. We analyzed whether fetal polymorphisms of the angiotensinogen (AGT) and angiotensin-converting enzyme genes influence birth weight and/or fetal total glycated hemoglobin (fTGH), a surrogate parameter of fetal insulin resistance at birth.
In 1132 white women delivering singletons, neonatal umbilical blood samples and clinical data of the mothers and newborns were obtained. Newborns were genotyped with respect to the AGT M235T and angiotensin-converting enzyme insertion/deletion polymorphism.
The AGT M235T TT polymorphism is associated with reduced birth weight (TT: 3288 g versus TM + MM: 3435 g, P < 0.05). Furthermore, newborns with a high percentage of fTGH (>6.5%) are more likely to have the TT genotype than those with normal fTGH (<or=6.5%, P < 0.05). With higher cutoffs for fTGH, the significance increases to P less than 0.005. No association was seen between these parameters and the fetal angiotensin-converting enzyme insertion/deletion phenotype.
The fetal AGT M235T polymorphism is associated with low birth weight and elevated fetal fTGH at birth. Previous findings show that elevated fetal fTGH correlates with low birth weight and that higher activity of the renin-angiotensin-aldosterone system is an independent risk factor for the development of diabetes mellitus and coronary artery disease. Therefore, our data are supportive of the fetal insulin hypothesis.
Journal of hypertension 04/2010; 28(4):732-9. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: It was suggested that fetal sex may substantially affect maternal glycemic control during pregnancy in genetically susceptible mothers. The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is known to affect glycemic control and may act in a sex-specific manner. This polymorphism is thus an attractive candidate to test this hypothesis using a second independent functionally relevant polymorphism. We analyzed the impact of fetal sex on maternal glycemic control during pregnancy in relation to the maternal PPARgamma2 Pro12Ala polymorphism. Two-thousand fourteen Caucasian women without preexisting diabetes and preexisting hypertension with singleton pregnancies delivering consecutively at the Charité obstetrics department were genotyped. Glycemic control was analyzed by measuring total glycated hemoglobin at birth. Correction for confounding factors and multiple testing was considered in the analysis. The maternal PPARgamma2 Pro12Ala polymorphism without consideration of fetal sex had no effect on blood pressure, new onset of proteinuria and total glycated hemoglobin at delivery. Mothers carrying both G alleles (GG genotype) delivering a girl had a higher (P = 0.015) total glycated hemoglobin (6.81 or - 0.50%) versus mothers carrying the same alleles but delivering boys (5.85 + or - 0.58%). Comparing mothers with the GG genotype delivering girls with mothers with CC or CG genotypes also delivering girls (6.32 + or - 0.72%) revealed a significantly higher maternal total glycated hemoglobin at delivery in the former group (P < 0.009). Fetal sex/sex chromosomes may substantially affect maternal glycemic control in mothers who are carriers of the GG alleles of the PPARgamma2 Pro12Ala polymorphism.
Pharmacogenetics and Genomics 02/2010; 20(2):139-42. · 3.61 Impact Factor