Ae. Barden et al., Association between the endothelin-1 gene Lys198Asn polymorphism blood pressure and plasma endothelin-1 levels in normal and pre-eclamptic pregnancy, J HYPERTENS, 19(10), 2001, pp. 1775-1782
Citations number
27
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objective This study examined the frequency of the Lys1 98Asn polymorphism
in the endothelin-1 (ET-1) gene in women with pre-eclampsia and normal preg
nancy; and its contribution to levels of plasma ET-1 and blood pressure.
Design and methods This was a retrospective study examining the frequency o
f the ET-1 Lys1 98Asn polymorphism in 72 proteinuric pre-eclamptics and 81
normal pregnant women. Height, weight, blood pressure and plasma ET-1 were
measured antenatally and at 6 weeks post-partum. Using specific mutagenic p
rimers, the frequency of the G/G (normal), G/T heterozygote and T/T (mutant
) genotypes of the Lys1 98Asn polymorphism were examined.
Results The polymorphism was not associated with preeclampsia. However, in
the combined pregnant groups after correction for BM I and group, a signifi
cant effect of the T-allele (T/T,G/T) on systolic blood pressure was found
(121 +/- 1.5 mmHg compared with 116 +/- 1.3 mmHg in the G/G homozygotes). A
significant interaction was found between the T-allele and pregnancy in de
termining systolic blood pressure, so that the effect was no longer seen po
st-partum. Pregnant women with the T/T genotype had significantly elevated
plasma ET-1 levels 5.8 pg/ml [confidence interval (Cl) 3.7-9.1] compared wi
th 3.1 pg/ml (Cl 2.6-3.8) in the G/T heterozygotes and 3.6 pg/ml (Cl 3.0-4.
1) in the normal G/G homozygotes.
Conclusion The Lys1 98Asn polymorphism does not directly contribute to the
incidence of pre-eclampsia. However, the association of the T-allele with r
aised blood pressure and the T/T genotype with increased plasma ET-1 levels
suggest that this polymorphism may interact with other genes or environmen
tal factors to sensitize pregnant women to develop pre-eclampsia. (C) 2001
Lippincott Williams & Wilkins.