H. Schunkert et al., ASSOCIATION BETWEEN A DELETION POLYMORPHISM OF THE ANGIOTENSIN-CONVERTING-ENZYME GENE AND LEFT-VENTRICULAR HYPERTROPHY, The New England journal of medicine, 330(23), 1994, pp. 1634-1638
Background. Epidemiologic studies have shown that left ventricular hyp
ertrophy is often found in the absence of an elevated cardiac workload
. To investigate whether such hypertrophy is determined in part by gen
etic factors, we studied the association between this condition, as as
sessed by electrocardiographic criteria, and a deletion (D)-insertion
(I) polymorphism of the angiotensin-converting-enzyme (ACE) gene. Meth
ods. A population-based random sample of 711 women and 717 men 45 to 5
9 years of age was studied cross-sectionally in Augsburg, Germany. Ele
ctrocardiographic indexes, including the Sokolow-Lyon index, Minnesota
Code 3.1, and the Rautaharju equations, were used to detect left vent
ricular hypertrophy. The status of the ACE gene with respect to the de
letion-insertion allele was determined by the polymerase chain reactio
n in all subjects with left ventricular hypertrophy and an identical n
umber of control subjects without the condition who were matched for a
ge, sex, and blood-pressure status. Results. We identified 141 women a
nd 149 men with evidence of left ventricular hypertrophy. Among these
subjects, an excess were homozygous for the D allele of the ACE gene (
odds ratio, 1.76; 95 percent confidence interval, 1.22 to 2.53; P = 0.
003). The association of the DD genotype with left ventricular hypertr
ophy was stronger in men (odds ratio, 2.63; 95 percent confidence inte
rval, 1.50 to 4.64; P<0.001) than in women and was most prominent when
blood-pressure measurements were normal (odds ratio, 4.05; 95 percent
confidence interval, 1.76 to 9.28; P = 0.001). This association was e
vident for each of the scores recorded in the electrocardiographic tes
ting for left ventricular hypertrophy.Conclusions. The findings sugges
t that left ventricular hypertrophy is partially determined by genetic
disposition. They identify the DD genotype of ACE as a potential gene
tic marker associated with an elevated risk of left ventricular hypert
rophy in middle-aged men.