The Lys198Asn polymorphism in the endothelin-1 gene is associated with blood pressure in overweight people

There is accumulating evidence that endothelin-l plays an important role in vascular pathophysiology. Our objective was to examine whether molecular v ariations at the endothelin-l locus were involved in susceptibility to myoc ardial infarction and variation in blood pressure. The entire coding sequen ce and 1.4 kb of the 5' flanking region were screened. Five polymorphisms w ere detected, which were genotyped in the ECTIM (Etude Cas-Temoin de l'Infa rctus du Myocarde) Study, a multicenter study comparing 648 male patients w ho had survived a myocardial infarction and 760 population-based controls. The polymorphisms were not associated with myocardial infarction, nor did t hey contribute to blood pressure levels in the population at large. However , a G/T polymorphism predicting an Lys/Asn change (ET1/C198) strongly inter acted (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 inde x 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 s ubjects (body mass index greater than or equal to 26 kg/m(2)), while no sig nificant effect was observed in lean subjects (body mass index <26 kg/m(2)) . To determine whether this finding could be replicated, the ET1/C198 was g enotyped in the Glasgow Heart Scan Study, a population-based study includin g 619 men and 663 women. Subjects homozygous for the T allele had higher re sting blood pressure levels than others (P<0.05). A similar interaction bet ween the T allele and body mass index was observed on the maximum blood pre ssure achieved during a treadmill exercise test (P<0.001). In conclusion, r esults from 2 independent studies suggest that the ET1/C198 polymorphism is associated with blood pressure levels in overweight people.