Influence of the M235T Polymorphism of Human Angiotensinogen (AGT) on Plasma AGT and Renin Concentrations after Ethinylestradiol Administration1
Michel Azizi,
Marie-Charlotte Hallouin,
Xavier Jeunemaitre,
Than Tam Guyene and
Joël Ménard
Centre d’Investigations Cliniques 9201 (M.A., M.-C.H.,
T.T.G., J.M.) and Laboratoire de Biologie Moléculaire (X.J.),
Assistance Publique des Hôpitaux de Paris (AP-HP) et INSERM,
Hôpital Européen Georges Pompidou, 75908 Paris,
France
Address all correspondence and requests for reprints to: Michel Azizi, Centre d’Investigations Cliniques 9201, Hôpital Européen Georges Pompidou, 20–40 rue Leblanc, 75908, Paris Cedex 15, France. E-mail: michel.azizi{at}egp.ap-hop-paris.fr
The T235 allele of the angiotensinogen (AGT) gene is associated
withplasma AGT concentration and pregnancy-induced hypertension.The
aim of this study was to compare changes in the circulating
renin-angiotensinsystem after short-term (2 days) and repeated (7
days) administrationof 50 µg ethinylestradiol (EE) in homozygous
normotensivemen (TT and MM). After repeated EE administration,
renin stimulationwas induced by a single oral dose of 40 mg
furosemide, followedby 50 mg captopril, 12 h later. The
short-term administrationof EE did not induce a significant
differential genotype-dependentincrease in AGT concentration. In the
7-day study, TT subjectshad higher peak plasma AGT concentrations than
MM subjects.The more pronounced AGT increase in TT subjects resulted
insimilar plasma renin activity at a lower plasma active renin
concentration,with a higher plasma renin activity/active renin ratio.
Thedifference between genotypes in renin secretion resulted in
readjustmentof angiotensins production. In conclusion, the T235 allele
ofthe AGT gene is associated with greater stimulation of AGT secretion
inplasma after EE administration. In the short-term, complete
readjustmentof the circulating renin-angiotensin system occurs,
througha decrease in renin release, which blunts the effects of the
increasein AGT concentration.
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