Full text of DOI:10.1177/000331970105200602

Angiology
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Differences in Frequency of the Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene in
Different Ethnic Groups
James Mathew, Khaja Basheeruddin and Suresha Prabhakar
ANGIOLOGY 2001 52: 375
DOI: 10.1177/000331970105200602
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375
in
Differences
ofthe Deletion
Frequency
ofthe
in
Polymorphism
Angiotensin-Converting
Gene
Ethnic
Different
Enzyme
Groups
James Mathew
MD, FACA, *†
Basheeruddin, PhD,‡
Khaja
Iowa
and Suresha
and
IL
Prabhakar, MD,‡
IA;
Galesburg
Chicago,
City,
A
characterized
the insertion or deletion of
a
Alu
in
serum
is
repeat
polymorphism
by
287-bp
sequence
determines about half the
intron 16 of the
angiotensin-converting enzyme gene
level
individuals. The deletion
angiotensin-converting enzyme
associated
variability among
polymorphism
with a
with
levels of
and
higher
angiotensin-converting enzyme
perhaps
polymorphism
the
greater
different
of
frequency
in
risk of cardiovascular diseases. The relative
of this
genetic
frequency
of this
was
to
compare
ethnic
is not known. The
objective
study
groups
angiotensin-converting enzyme gene
Angiotensin-converting enzyme genotype
workers of three different ethnic
in different ethnic
insertion/deletion
polymorphism
groups.
in
was determined
middle-aged healthy hospital
and
There were
Indians).
(African
whites,
Americans,
origins
142 African
136
and 82 whites. The distribution of the
Americans,
Indians,
deletion-deletion,
in
and insertion-insertion
African Americans
and
and
(29%, 60%,
and
whites
(29%, 40%,
insertion-deletion,
respectively),
11 %,
31 %,
genotypes
Indians
and
(19%, 50%,
31 %,
respectively)
=
was
different
<
The
of the deletion
allele among
0.005).
respectively)
African
significantly
(p
frequency
and whites
and
0.44,
wasalso
Americans,
(0.59, 0.49,
Indians,
respectively)
significantly
=
different
African Americans had the
of deletion allele and the
0.05).
(p
highest frequency
the three
lowest
of the insertion-insertion
of the
The
frequency
frequency
genotype among
groups.
is different
of the deletion
polymorphism
Americans, whites,
angiotensin-converting enzyme gene
among
African
This
in
and Indians.
be
relation to the risk of
high
may
important
and
in
in
cardiovascular
African Americans and
be relevant
morbidity
mortality
diseases in
may
This
explaining
emphasizes
in
also
differences
the
cardiovascular
different
populations.
angiotensin-converting enzyme
finding
in
of
importance
studying
populations.
gene polymorphism
these
genetically
need
of
small size of
this
Because
the
however,
homogenous
study,
findings
further confirmation.
Introduction
2001
52:375-379,
the*Division of
Angiology
From
of
Medicine,
Cardiology, Department
The
ease
features ofischemic heart dis-
epidemiologic
of
Iowa
of
Iowa
’LaSalle
IA;
Medicine,
University
College
City,
in different
dif-
Whereas
and
IL;
County
Cardiology
and
Galesburg Cottage Hospital, Galesburg,
vary
populations.1,2
of
IL
Medicine Cook
and
+Departments
Pathology
in
ferences
the
and
ofrisk fac-
and so-
prevalence
impact
Chicago,
Hospital,
other diseases in the
tors,
community,
North
695
James
61401
Street,
MD,
Mathew,
Kellog
Correspondence:
cioeconomic factors
all be
in this
important
may
IL
E-mail:
Galesburg,
&copy;2001
Glen
manthi@galesburg.net
in
differences
and
regard,
predisposition
genetic
to diseases cannot be excluded.
Westminster
Glen Cove
Avenue,
708
Publications, Inc.,
Head, NY
USA
11545,
susceptibility
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376
African Americans seem to have
of
a
lower
of LVH. One
neurohormon-
velopment
important
al factor that
dis-
causes LVHis
II.
prevalence
angiographic coronary artery
angiotensin
than whites.3~4
this
African
cardio-
II is
action of an-
the
ease
formed
fact,
Angiotensin
Despite
by
have
a
similar or
and
risk of
Americans
vascular
diac death
on
(ACE)
higher
giotensin-converting
angioten-
enzymes
characterized
of
and
sin I. A
suddencar-
in whites.4
insertion
morbidity
mortality,
polymorphism
by
4
with
or deletion
a
Alu
se-
(I)
quence
(D)
compared
findings
287-bp
repeat
in
Factors other than
disease
intron 16 of human ACE
is re-
angiographic coronary artery
gene
level variabil-
for
be involved in the risk of
about halfof the
ACE
therefore,
may,
sponsible
cardiac
individuals.~The D
cardiovascular disease and sudden
death
is
ity among
polymorphism
associated with
a
level ofACE.
D
The
in African Americans.
higher
poly-
Left ventricular
is an in-
is more
whites. 4,6
has been
increased risk
to be associated
(LVH)
and
morphism
reported
hypertrophy
of
with an
ofLVHand
in-
dependent predictor
mortality’
myocardial
There are no
in
common in African Americans than
farction in certain
populations.8~9
on
disease and
data
the
ofACE
systemic hyperten-
Coronary artery
frequency
gene polymorphism
can lead to the
of LVH.
in African Americans
in
of Indian
ori-
sion
or
development
persons
was to
Neurohormonal factors can also
the de-
The
of this
promote
gin.
objective
study
compare
I.
ofAfrican
Clinical characteristics
whites and Indians.
Table
Americans,
<
the three
or
0.01
of
test for overall difference
i Mean
stress test.
SD.
by
among
*p
chi-square
infarction,
groups.
positive
disease,
angiographic coronary
myocardial
history
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377
the ACE
in
Clinical variables and
the
of
the three
Clinical variables
vs those in sub-
distribution
ethnic
genotypes
persons
whites
genotypes
compared.
among
African
of
in
ethnic
in
were
three
the United
Americans,
groups
with
groups:
States,
and
of
in
the
ID/DD
genotype
genotype
compared; p <_
persons
origin
subjects
with the II
were also
within
0.05
each ethnic
chi-square
by
Indian subcontinent.
jects
group
discrete variables andt test for continuous
test for
variables were considered
The institutional review board of Cook
statistically significant.
County
the
The
Methods
Hospital approved
informed consent.
study.
participants
gave
at
The
were
the Cook
employees
study subjects
in
to
IL.
Chicago,
Apparently
were eli-
age
County Hospital
of
20
55
healthy persons
years
Thevolunteers
a
to
completed
gible
participate.
measured the
The
Results
investigators
questionnaire.
blood
and heart rate. African
defined as self-identified
pressure
I
Table shows the clinical variables of the
Americans were
study
82
African
African
There were
Americans of
eration
142
and 136 Indians.
Americans,
subjects.
origin excluding first-gen-
White Americans of
and
whites,
Height, weight,
sys-
immigrants.
were identified as whites. Since
ofIndian or Pakistani
tolic blood
were
different
0.05 for over-
pressure
three ethnic
significantly
European origin
in the
groups
the three ethnic
persons
origin living
amongthe
all difference
each of these
cant differences in the
ables in the three
(p<
a
common ethnic
for
United States have
among
variables).
ancestry,
groups
are defined as Indians.
There were no
signifi-
they
determined
analysis
of other vari-
The ACE
was
genotype
chain reaction
by poly-
frequency
II
shows the
genotypes
on DNA
iso-
merase
(PCR)
groups.
lated from
The PCR
blood mononuclear cells.
Table
in the three
peripheral
products
were
elec-
ethnic
was
The distribution ofthe
different
separated by
and identified
groups.
genotypes
the three
among
on 2%
bromide
insertion-insertion
by
agarose gel
significantly
trophoresis
Individuals with the
African Americans had the
ethidium
0.005).
frequency
groups (p <
staining.
<
had
PCR
lowest
of the II
0.003
(II)
genotype
490-bp
genotype (p
individuals with the deletion-deletion
for the overall
three ethnic
difference amongthe
products,
(DD)
had
PCRproduct, and in-
African Americans also had the
highest
groups
genotype
190-bp
groups).
D
allele
amongthe
three
dividuals with the insertion-deletion
ofthe
(ID)
products.’
geno-
frequency
in
the
of D
had both
and
PCR
The difference
490-
0.05).
type
190-bp
(p =
frequency
Table II. ACE
in African
whites and Indians.
Americans,
genotype
<
the
three
0.005 for the distribution of the
*p
’ p
genotype among
groups.
of
in the
D
the
allele
amongthe three
difference
test for the
0.05
groups.
by chi-square
frequency
Downloaded from ang.sagepub.com at FLORIDA ATLANTIC UNIV on November 20, 2014

378
D
allele was
Americans
whites and
significant betweenAfrican
ofthe ACE
therefore,
of
statistically
polymorphism
gene may,
increased
<
and Indians
Indians
andbetween
be mediated
an
0.001)
(p
through
production
II or
but not between
an enhanced
(p
<
0.03),
angiotensin
through
degrada-
<
Americans and whites
There
tion of
African
were no
0.08).
(p
bradykinin. 15
main
differences in the
The
limitation of the
is its rela-
re-
study
with
in
our
statistically significant
in
with
of
small size.
of clinical variables
frequency
persons
with
tively
Compared
previous
had
a
the white
the
the
not
ID/DD
ports,?,8,12
study
genotype compared
persons
subjects
be-
be
may
are not
II
within
ethnic
lower
ofthe allele. This
D
any
group (analysis
frequency
genotype
shown).
cause the whites in
different studies
ge-
be
it
netically homogenous. Alternatively,
may
the
sizes
because estimates of
of alleles
be reliable.
frequency
may
from
not
small
sample
the
did not have
to detect differences in clinical events in
Furthermore,
power
persons
ethnic
study
adequate
Discussion
shows
of different ACE
within each
genotypes
that the distribution of ACE
This
study
group.
amongAfrican
Therefore,
is different
Americans,
important
genotypes
it is
and Indians.
that studies of
whites,
and
be con-
gene polymorphismin general
in
ofACE
ducted
gene polymorphism
particular
in
homogenous populations.
genetically
The differences in the distribution of ACE
geno-
Conclusion
in
be an
risk of cardiovascular
factor
the relative
type may
important
in
and
The distribution ofthe ACEgenotypes is different
morbidity
mortality
different
in African
and Indians. These
of
Americans,
whites,
populations.
The
of the
D
the
higher frequency
polymorphism
findings emphasize
importance
studying
in African Americans in this
is not re-
study
ACE
nous
in
seen
gene polymorphism
genetically homoge-
blood
in this
lated to the
higher systolic
pressure
populations.
enzyme
Angiotensin-converting
studies have shown that
be
a
relevant factor in
because
previous
gene polymorphism may
group
there is no correlation between ACE
differences in the
features of is-
gene poly-
epidemiologic
It
in
different
and blood
African Americans
is known that
chemic heart disease
African Americans seem to have
morphism
pressure.10
populations.
a
have
a
of
cardiac
fre-
with
greater prevalence
higher
of
of D
the
LVH and
death
a
sudden
of
higher proportion
quency
polymorphism compared
This
a
lower
the other ethnic
tant factor in the
and
be an
may
despite
prevalence
angiographic
groups.
impor-
4
disease
with whites.4
risk ofcardiovascularmor-
compared
high
coronary artery
D
of the ACE
has been
in African
The
Americans.
polymorphism
gene
bidity
mortality
to be associated with anincreased risk of
There
Because of the small size of the
however,
reported
study,
need further confirmation.
LVH
these
is, however,
by electrocardiography.8
findings
evidence for its association with
LVH. 11,12 The
contradictory
echocardiographic
greater frequen-
D
of
have
ofthe
ACE
cy
an
gene may
polymorphism
the
ofLVHand
andmortal-
role in
pathogenesis
important
risk ofcardiovascular
morbidity
high
in African
Americans.
ity
Acknowledgments
the
Angiotensin-converting enzyme catalyzes
as the
Ali J.
made
sisted in
of
II as well
MD reviewed the
and
E.
Pritchett as-
Marian,
synthesis
angiotensin
degra-
manuscript
II is
a
dation of
valuable remarks.
Angiotensin
power-
bradykinin.
Stephanie
acts as
a
factor for
the vascular smooth
and
of
the
ful vasoconstrictor and
growth
preparation
Sahib
manuscript. Jyothi
both the
muscle cells.~
Rohit
Mohanti,
MD;
John
MD;
Saddi, MD;
Sundarani,
myocardium
is
of the
levels ofACE
as well as in
a
and
MD
collected data.
the other
On
hand,
polymorphism
higher
Shivaram,
bradykinin
Deepak
The
D
VR
and
vasodilator.’
Dharmavarapu, MDassist-
Lee,
BSc,
potent
in
ed
with
tests. Prasad
ACE
in
is associated
the PCR
Kilaru, MD
gene
performing
in
in Tlymphocytes 13
Monica
Peck
gave
the
the
and
statistical
We thank our
assistance.
helped
analysis.
plasma
myocardium.l4
risk
LVH
The increased
of
and
secretarial
colleagues
with the
who
associated
for this
volunteered
other cardiovascular diseases
study.
Downloaded from ang.sagepub.com at FLORIDA ATLANTIC UNIV on November 20, 2014

379
left ven-
and
angiotensin-converting-enzyme gene
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