title: The Glu298Asp variant of the endothelial nitric oxide synthase gene is associated with an increased risk for abruptio placentae in pre-eclampsia.
abstract: Attempts to define a pre-eclampsia susceptibility profile have been hampered by the wide clinical spectrum of the condition and the complex genetics underlying it. Genes that modulate blood pressure, fluid homeostasis and placental vascular development have been considered plausible candidates. Among these are the angiotensinogen (AGT) gene variant Met235Threo, which has been associated with pre-eclampsia and the endothelial nitric oxide synthase (eNOS) polymorphism Glu298Asp, which has been associated with both pre-eclampsia and abruptio placentae, a condition that often co-exists with pre-eclampsia. The aim of this study was to investigate a potential association between these gene variants and pre-eclampsia with and without abruptio placentae in a South African patient group. Fifty primigravidas with early onset, severe pre-eclampsia, 50 women presenting primarily with abruptio placentae (whether associated with pre-eclampsia or not) and a control panel of 50 healthy pregnant women constituted the study groups. The Met235Threo and Glu298Asp variants were characterised by polymerase chain reaction and restriction enzyme analysis. No association was demonstrated between the M235T variant of the AGT gene and pre-eclampsia or abruptio placentae. In contrast, the combined frequency of the eNOS variant genotypes (GT and TT) was significantly higher in the abruptio placentae group (49%) than the control group (21%) (p=0.006). Furthermore, in the pre-eclampsia patients who subsequently developed abruptio placentae, the eNOS GT genotype emerged as a major risk factor for the development of abruptio placentae (p<0.0001). These data suggest that the presence of a Glu298Asp eNOS variant may pre-dispose a pre-eclamptic woman to develop abruptio placentae or that it is a marker for predisposition.
authors.affiliation: Department of Genetics, Stellenbosch University, Private Bag X1, Matieland, 602, South Africa. rhillerm@sun.ac.za.
authors.forename: Renate
authors.initials: R
authors.lastname: Hillermann
authors.affiliation: Department of Obstetrics and Gynaecology and MRC Unit forPerinatal Mortality, Faculty of Health Sciences, Tygerberg Campus, Stellenbosch University, South Africa.
authors.forename: Kashefa
authors.initials: K
authors.lastname: Carelse
authors.affiliation: Department of Obstetrics and Gynaecology and MRC Unit forPerinatal Mortality, Faculty of Health Sciences, Tygerberg Campus, Stellenbosch University, South Africa.
authors.forename: G Stefan
authors.initials: GS
authors.lastname: Gebhardt
mesh_terms: D000037:Abruptio Placentae / Q000201:enzymology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D015183:Restriction Mapping; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III