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Risk Of Pre-Eclampsia As Much Paternal As Maternal

The risk of pre-eclampsia is just as likely to be inherited from fathers as it is from mothers.

Findings of a gene responsible for producing an important detoxifying enzyme (GSTP1) add weight to the theory that an imbalance in toxic compounds and detoxifying enzymes increases susceptibility to the disorder, declare the authors of this paper.

The researchers point out that pre-eclampsia has a still obscure aetiology. A major feature is placental maladaptation, probably because of inadequate invasion of fetal trophoblast cells in the myometrium and spiral arteries that might be related to local oxidative stress. Reactive oxygen species (ROS), lipid peroxides, and other toxic compounds are metabolized by biotransformation enzymes in scavenging and detoxifying processes.

Increasing evidence suggests an important function of antioxidants and detoxification enzymes in pre-eclampsia.

These researchers recently proposed that the 105I1eŪVal polymorphisms in the glutathione S-transferase P1 gene (GSTP1), associated with lower enzyme detoxification capacity, enhanced maternal susceptibility to pre-eclampsia. As placenta is of fetal origin and therefore characterized by both maternal and paternal contribution, the risk for pre-eclampsia might be modified by maternal as well as paternal genetic variations in detoxification activities.

The researchers investigated GSTP1 polymorphisms in a cohort of 113 pre-eclampsia trios (mother, father, baby) in which the mothers had suffered pre-eclampsia. A control cohort of 149 men and 168 women was recruited.

Pre-eclampsia was defined as the occurrence after 20 weeks' gestation of a diastolic blood pressure greater than 90 mmHg and concordant proteinuria (urinary protein greater than 0.3 g/l in a 24 hour collection period or a protein/creatinine ratio greater than 0.3 g/10 mmol).

Analysis of the blood samples showed that abnormalities in the GSTP1 gene were significantly more common in families affected by pre-eclampsia than among controls. Fathers were as likely as mothers in the affected families to carry the genetic abnormality, increasing the risk of any resulting children also carrying the genetic defect.

The Val 105 allele was present significantly more often in mothers (0.32), fathers (0.37), and offspring (0.38) of pre-eclamptic pregnancies compared with the frequency in controls (0.22). Comparisons of GSTP1 genotypes and allele frequencies between pre-eclampsia mothers, fathers, and offspring showed no statistically significant differences.

"We now show that this polymorphism in GSTP1 in paternal and fetal genes, in addition to the earlier reported association between pre-eclampsia and this polymorphism in the maternal genome, may contribute to the risk for pre-eclampsia," the researchers declare.

"Furthermore, we were able to confirm linkage disequilibrium of pre-eclampsia with the Val 105 allele, again strongly suggesting that the GSTP1 polymorphism is indeed associated with the disease."

This is in this accordance with other recent findings that both men and women who were the product of a pregnancy complicated by pre-eclampsia were significantly more likely than control men and women to have a child who was also the product of a pregnancy complicated by pre-eclampsia.

"To our knowledge, this is the first polymorphism in the paternal genome related to pre-eclampsia," the investigators conclude. "Higher frequencies of the Val 105 allele in pre-eclampsia might result in a lower detoxification capacity in the trophoblast and inadequate coping with local oxidative stress, resulting in a higher susceptibility to pre-eclampsia."

This study was undertaken by Dr Eric Steegers and colleagues Department of Obstetrics and Gynaecology, Erasmus University Medical Centre, Rotterdam, The Netherlands. Collaborating colleagues were with the Department of Obstetrics and Gynecology, University Medical Center, Nijmegen, The Netherlands.
Journal Of Medical Genetics 2002; 39: 44-5.

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