A Common Genetic Variant of the Angiotensin Converting Enzyme(ACE) Gene and Pregnancy InducedHypertensive Disorders.
- Author:
Cheong Rae ROH
1
;
Duk Kyung KIM
;
Byung Koo YOON
;
Soon Ha YANG
;
Jae Hyun CHUNG
;
Duk Soo BAE
;
Je Ho LEE
Author Information
1. Department of Obstetrics and Gynecology, Samsung Seoul Hospital, Samsung Medical Center, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Angiotensin converting enzyme gene;
Polymorphism;
Pregnancy induced hypertension
- MeSH:
Alleles;
Angiotensin II;
Angiotensins*;
Autacoids;
Diagnosis;
DNA;
Eclampsia;
Electrophoresis;
Female;
Follow-Up Studies;
Genotype;
Gynecology;
Homozygote;
Humans;
Hypertension;
Hypertension, Pregnancy-Induced;
Introns;
Obstetrics;
Peptidyl-Dipeptidase A;
Plasma;
Polymerase Chain Reaction;
Postpartum Period;
Pre-Eclampsia;
Pregnancy*;
Proteinuria;
Renin-Angiotensin System;
Vasoconstriction
- From:Korean Journal of Obstetrics and Gynecology
1997;40(6):1189-1199
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: The angiotensin coverting enzyme(ACE) gene(encoding kininase II, EC3.4.15.1) contains a polymorphism based on the presence(insertion [I]) or absence(deletion[D]) within an intron of a 287bp nonsense DNA domain, resulting in three genotypes(D/I) and I/I homozygotes, and I/D heterozygotes). Alu insertion is associated with lowerACE level than deletion allele(D) and it was observed that D/D individuals have twice theACE activity of I/I patients. Pregnancy induced hypertension(PIH) probably results fromdominating pressor systems owing to loss of antagonizing vasodilator autacoids. AngiotensinII is an extremely potent arteriolar vasoconstrictor. Overactivity or failure to supressresponsiveness to the increased activity of angiotensin II, which is generated by ACE,would seem to be a reasonable basis for the vasoconstriction of PIH. The aim of this studyis to evaluate the relationship between ACE genotype and PIH. METHODS: Blood sampling was taken from 39 patients with PIH. The hypertensivedisorders, confirmed at postpartum follow up, were classified as gestational hypertensionwithout proteinuria, preeclampsia(mild and severe) and eclampsia. The diagnosis ofpreeclampsia was made according to the American College of Obstetrics and Gynecology criteriaof hypertension and proteinuria(>300 mg/24 hr urine). Genomic DNA was extractedfrom blood sample. After PCR amplification of the respective fragments from intron 16 ofthe ACE gene, size fractionation and visualization by electrophoresis were performed. RESULTS: PIH group(including gestational hypertension, mild and severe preeclampsia: frequency of I allele 0.756 and D allele 0.244) had more I allele and less D allele whencompared with normal population(frequency of I allele 0.609 and D allele 0.391)(p < 0.05).And PIH group had more I/I homozygote individuals showing significant distortion fromHardy-Weinberg equilibrium of ACE genotype(p < 0.05). Moreover, severe preeclampsiagroup alon(frequency of I allele 0.759 and D allele 0.241) had more I allele and less Dallele when compared with normal population and had significantly more I/I homozygoteindividuals. CONCLUSION: As pregnancies with PIH had more ACE I allele and I/I homozygoteindividuals. PIH could be associated with I allele of the ACE gene. Considering the observedcodominant association between the D-I polymorphism and plasma ACE activity, our resultis in favor of the thesis that PIH primarily arises from defective synthsis of vasodilatingautacoids and renin-angiotensin system exerts secondary vasoconstrictive action. However,the relationship between ACE genotype and defective vasodilating mechanism during pregnancyis unknown at present.
