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 pregnancy; and its contribution to levels of plasma ET-1 and blood pressure.Design and methods This was a retrospective study examining the frequency of 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 primers, 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 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 (Cl) 3.7-9.1] compared with 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 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. (C) 2001 Lippincott Williams & Wilkins.