Angiotensin-converting enzyme and angiotensinogen gene polymorphisms are non-randomly distributed in oral contraceptive-induced hypertension.
OBJECTIVE
Oral contraceptives (OC) usage increases serum angiotensinogen levels to three to five times normal and about 5% of these women develop arterial hypertension. The genetic contribution to this susceptibility to OC-induced hypertension is poorly understood. We have analyzed the genotypes of 149 hypertensive and 101 normotensive women using oral contraceptives, for three genetic polymorphisms in genes of the renin-angiotensin system: an insertion/deletion (I/ D) in the angiotensin converting enzyme (ACE) gene, the T235M polymorphism of the angiotensinogen gene (AGT) and a point mutation in its promoter.


RESULTS
After cessation of oral contraception the mean arterial pressures of the hypertensive women were separable into two non-overlapping groups; 88 of the women remained hypertensive and 61 returned to normal blood pressure. Both groups of hypertensive women had a similarly higher frequency of hypertensive relatives than the normotensive women, but were otherwise similar. The 235T allele of AGT was significantly increased in frequency in the 61 oral contraceptive-inducible hypertensive women compared with the controls and the 88 women that remained hypertensive. The ACE I/D genotypes were similarly distributed within the three groups of women, but were distinctly non-random in the oral contraceptive-induced hypertensive women when they were also classified by AGT genotype.


CONCLUSIONS
This statistical interaction of genotype frequencies suggests that the genetic basis of susceptibility to OC-induced hypertension is complex.
Mulatero
P
P
Department of Medicine and Experimental Oncology, San Vito Hospital, University of Torino, Italy. mailto:mulatero@tin.it
Rabbia
F
F
di Cella
S M
SM
Schiavone
D
D
Plazzotta
C
C
Pascoe
L
L
Veglio
F
F
D000328:Adult; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics*; D003276:Contraceptives, Oral / Q000009:adverse effects*; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*; D012016:Reference Values
D003276:Contraceptives, Oral; D004251:DNA Transposable Elements; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A