ENHANCED PRESSOR-RESPONSE TO ANGIOTENSIN-I IN NORMOTENSIVE MEN WITH THE DELETION GENOTYPE (DD) FOR ANGIOTENSIN-CONVERTING ENZYME

被引：188

作者：

UEDA, S

ELLIOTT, HL

MORTON, JJ

CONNELL, JMC

机构：

[1] UNIV GLASGOW,WESTERN INFIRM,DEPT MED & THERAPEUT,GLASGOW G11 6NT,LANARK,SCOTLAND

[2] WESTERN INFIRM & ASSOCIATED HOSP,MRC,BLOOD PRESSURE UNIT,GLASGOW G11 6NT,LANARK,SCOTLAND

来源：

HYPERTENSION | 1995年 / 25卷 / 06期

关键词：

ANGIOTENSIN-CONVERTING ENZYME; ALLELES; ANGIOTENSIN I; ANGIOTENSIN II;

D O I：

10.1161/01.HYP.25.6.1266

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

The insertion (I)/deletion (D) polymorphism of the human angiotensin-converting enzyme gene has emerged as a genetic risk factor for ischemic heart disease. However, the functional consequences of this polymorphism in humans are not known. Ten normotensive men with the DD genotype and 10 with the II genotype participated in a study in which presser responses to stepwise infusions of incremental doses of angiotensin I (Ang I) and Anp; II and Ang II production during Ang I infusion were measured. Presser responses were expressed as PD20, which reflects the angiotensin dose required to raise mean blood pressure by 20 mm Hg. The PD20 for Ang I in subjects with the DD genotype was significantly lower than that in II genotype subjects (8.8 versus 14.8 ng/kg per minute, P=.0091), where the PD20 for Ang II between the two groups did not differ significantly. The ratio of PD20 for Ang I and Ang Il in DD subjects was significantly lower than that in II subjects (0.85 versus 0.96, P=.0452), and the venous levels of Ang II during Ang I infusion in DD subjects were significantly higher than those in II subjects (P<.01). Our study has shown increased presser responsiveness to Ang I, probably as a consequence of the generation of increased Ang II levels, in subjects homozygous for the DD allele of the angiotensin-converting enzyme gene. This result may be relevant to the reported adverse cardiovascular risk conferred by the D allele, as it provides a mechanistic rationale for the association between this polymorphism cardiovascular disease.

引用

页码：1266 / 1269

页数：4

共 20 条

[1] Cambien F., Poirier O., Lecerf L., Evans A., Cambou J.P., Arveiler D., Luc G., Bard J.M., Bara L., Richard S., Tiret L., Amouyel P., Alhenc-Gelas F., Soubrier F., Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction, Nature, 359, pp. 641-644, (1992)
[2] Tiret L., Kee F., Poirier O., Nicaud V., Lecerf L., Evans A., Cambou J.P., Arveiler D., Luc G., Amouyel P., Cambien F., Deletion polymorphism in angiotensin-converting enzyme gene associated with parental history of myocardial infarction, Lancet, 341, pp. 991-992, (1993)
[3] Evans A.E., Poirier O., Kee F., Lecerf L., McCrum E., Falconer T., Crane J., O'Rourke D.F., Cambien F., Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease, Q J Med, 87, pp. 211-214, (1994)
[4] Ohnishi M., Fujii K., Minamino T., Higaki J., Kamitani A., Rakugi H., Zhao Y., Mikami H., Miki T., Ogihara T., A potent genetic risk factor for restenosis, Nat Genet, 5, pp. 324-325, (1993)
[5] Schunkert H., Hense H.W., Holmer S.R., Slender M., Perz S., Keil U., Lorell B.H., Riegger G.A., Association between a deletion polymorphism of the angiotensin-converting enzyme gene and left ventricular hypertrophy, N Engl J Med, 330, pp. 1634-1638, (1994)
[6] Morris B.J., Zee R.Y.L., Schrader A.P., Different frequencies of angiotensin-converting enzyme genotypes in older hypertensive individuals, J Clin Invest, 94, pp. 1085-1089, (1994)
[7] Rigat B., Hubert C., Alhenc-Gelas F., Cabbein F., Corvol P., Soubrier F., An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels, J Clin Invest, 86, pp. 1343-1346, (1990)
[8] Tiret L., Rigat B., Visvikis S., Brenda C., Corvol P., Cambien F., Soubrier F., Evidence from combined segregation and linkage analysis, that a variant of the angiotensin 1-converting enzyme (ACE) controls plasma ACE levels, Am J Hum Genet, 51, pp. 197-205, (1992)
[9] Harrap S.B., Davidson H.R., Conner J.M., Soubrier F., Corvol P., Fraser R., Foy C.J., Watt G.C., The angiotensin I converting enzyme gene and predisposition to high blood pressure, Hypertension, 21, pp. 455-460, (1993)
[10] Jeunemaitre X., Lifton R.P., Hunt S.C., Williams R.R., Lalouel J.-M., Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension, Nat Genet, 1, pp. 72-75, (1992)

← 1 2 →