Association between the endothelin-1 gene Lys198Asn polymorphism blood pressure and plasma endothelin-1 levels in normal and pre-eclamptic pregnancy.
OBJECTIVE
This study examined the frequency of the Lys198Asn polymorphism in the endothelin-1 (ET-1) gene in women with pre-eclampsia and normal pregnancy; and its contribution to levels of plasma ET-1 and blood pressure.


METHODS
This was a retrospective study examining the frequency of the ET-1 Lys198Asn 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 primers, the frequency of the G/G (normal), G/T heterozygote and T/T (mutant) genotypes of the Lys198Asn polymorphism were examined.


RESULTS
The polymorphism was not associated with pre-eclampsia. However, in the combined pregnant groups after correction for BMI and group, a significant 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 determining systolic blood pressure, so that the effect was no longer seen post-partum. Pregnant women with the T/T genotype had significantly elevated plasma ET-1 levels 5.8 pg/ml [confidence interval (CI) 3.7-9.1] compared with 3.1 pg/ml (CI 2.6-3.8) in the G/T heterozygotes and 3.6 pg/ml (CI 3.0-4.1) in the normal G/G homozygotes.


CONCLUSIONS
The Lys198Asn polymorphism does not directly contribute to the incidence of pre-eclampsia. However, the association of the T-allele with raised blood pressure and the T/T genotype with increased plasma ET-1 levels suggest that this polymorphism may interact with other genes or environmental factors to sensitize pregnant women to develop pre-eclampsia.
Barden
A E
AE
University of Western Australia, Department of Medicine, Royal Perth Hospital, Perth, Australia. abarden@cyllene.uwa.edu.au
Herbison
C E
CE
Beilin
L J
LJ
Michael
C A
CA
Walters
B N
BN
Van Bockxmeer
F M
FM
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D001794:Blood Pressure / Q000502:physiology*; D019332:Endothelin-1 / Q000097:blood* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology*; D049590:Postpartum Period / Q000502:physiology; D011225:Pre-Eclampsia / Q000097:blood / Q000503:physiopathology*; D011247:Pregnancy / Q000097:blood / Q000502:physiology*; D012016:Reference Values
D019332:Endothelin-1