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(Hypertension. 1999;33:1169-1174.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
The Lys198Asn Polymorphism in the Endothelin-1 Gene Is Associated With Blood Pressure in Overweight People
From INSERM U525 (L.T., O.P., F.C.); INSERM SC7 (V.H.); Cardiology Department and MRC Clinical Research Initiative in Heart Failure, Western Infirmary and University of Glasgow (UK) (T.McD., J.J.V.McM., H.J.D.); Scottish MONICA Project, Glasgow Royal Infirmary (UK) (C.M.); MONICA Project in Bas-Rhin, France (D.A.), Haute-Garonne, France (J.B.R.), Lille, France (G.L.), and Belfast, UK (A.E.).
Abstract—There is accumulating
evidence that endothelin-1 plays an important role in vascular
pathophysiology. Our objective was to examine whether molecular
variations at the endothelin-1 locus were involved in susceptibility to
myocardial infarction and variation in blood pressure. The entire
coding sequence and 1.4 kb of the 5' flanking region were screened.
Five polymorphisms were detected, which were genotyped in
the ECTIM (Etude Cas-Témoin de l'Infarctus du Myocarde) Study, a
multicenter study comparing 648 male patients who had survived a
myocardial infarction and 760 population-based controls. The
polymorphisms were not associated with myocardial infarction, nor
did they contribute to blood pressure levels in the population at
large. However, a G/T polymorphism predicting an Lys/Asn change
(ET1/C198) strongly interacted (P<0.001) with body mass
index in the determination of blood pressure levels. There was a
steeper increase of blood pressure with body mass index in carriers of
the T allele than in GG homozygotes.
As a consequence, the T allele was associated with
an increase of blood pressure in overweight subjects (body mass index
26 kg/m2), while no significant effect was observed in
lean subjects (body mass index <26 kg/m2). To determine
whether this finding could be replicated, the ET1/C198 was
genotyped in the Glasgow Heart Scan Study, a population-based
study including 619 men and 663 women. Subjects homozygous for the
T allele had higher resting blood pressure levels
than others (P<0.05). A similar interaction between the
T allele and body mass index was observed on the
maximum blood pressure achieved during a treadmill exercise test
(P<0.001). In conclusion, results from 2 independent
studies suggest that the ET1/C198 polymorphism is associated with
blood pressure levels in overweight people.
Key Words: genes • endothelin • myocardial infarction • hypertension, genetic • blood pressure • body mass index • obesity
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