FUNCTIONAL AND GENETIC-STUDIES OF THE ANGIOTENSIN-II TYPE-1 RECEPTOR IN PREECLAMPTIC AND NORMOTENSIVE PREGNANT-WOMEN

Objective To examine and compare angiotensin II type 1 receptor genoty pe and its relationship to platelet angiotensin II binding for pre-ecl amptic and normotensive pregnant women. Design In a case-control study , 43 pre-eclamptic women and 83 normotensive women were genotyped at t he angiotensin II type 1 receptor gene locus. Platelet angiotensin II binding was measured for a subset of 11 pre-eclamptic and 57 normotens ive pregnant women. We genotyped 162 healthy blood donors also, to exa mine the allelic background and patterns of linkage disequilibrium in the Nottingham population. Methods Patients were recruited during preg nancy using a rigorous definition of pre-eclampsia. DNA was extracted from peripheral venous blood and genotyped at six previously described diallelic polymorphisms in the angiotensin II type 1 receptor gene, u sing competitive allele-specific oligonucleotide hybridization, and at a dinucleotide repeat polymorphism in the 3' flanking region of the g ene. Platelet angiotensin II binding and plasma angiotensin II concent rations were determined for peripheral venous blood. Results Normotens ive pregnant women homozygous for cytosine at nucleotide 573 had signi ficantly higher levels of platelet angiotensin II binding than did het erozygous women and women homozygous for thymidine at this site. Pre-e clamptic women had significantly higher levels of platelet angiotensin II binding than did normotensive pregnant women. The frequencies of a llelic variants did not differ significantly between normotensive and preeclamptic women. Conclusion The physiological regulation of platele t angiotensin II type 1 receptor expression in normal pregnancy is det ermined in part by angiotensin II type 1 receptor genotype. There was no evidence that the polymorphisms in the angiotensin II type 1 recept or gene were associated with pre-eclampsia.