Association between the endothelin-1 gene Lys198Asn polymorphism blood pressure and plasma endothelin-1 levels in normal and pre-eclamptic pregnancy

• Published in: Journal of hypertension Vol. 19; no. 10; p. 1775
• Main Authors: Barden, A E, Herbison, C E, Beilin, L J, Michael, C A, Walters, B N, Van Bockxmeer, F M
• Format: Journal Article
• Language: English
• Published: England 01.10.2001
• Subjects: Adult; Alleles; Amino Acid Sequence - genetics; Blood Pressure - physiology; Endothelin-1 - blood; Endothelin-1 - genetics; Female; Gene Frequency; Genotype; Humans; Polymorphism, Genetic - genetics; Polymorphism, Genetic - physiology; Postpartum Period - physiology; Pre-Eclampsia - blood; Pre-Eclampsia - physiopathology; Pregnancy - blood; Pregnancy - physiology; Reference Values
• ISSN: 0263-6352
• DOI: 10.1097/00004872-200110000-00011

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. 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. 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. 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.