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Rheumatic heart disease in Uganda: the association between MHC class II HLA DR alleles and disease: a case control study.
[acute rheumatic fever]
Rheumatic
heart
disease
(
RHD
)
,
the
only
long
term
consequence
of
acute
rheumatic
fever
,
remains
a
leading
cause
of
morbidity
and
mortality
among
young
adults
in
Uganda
.
An
inherited
susceptibility
to
acute
rheumatic
fever
centers
around
the
major
histocompatibility
class
II
human
leucocyte
antigens
.
However
,
there
is
paucity
of
data
from
sub-
Saharan
Africa
.
This
study
compares
the
frequency
of
HLA
class
II
DR
alleles
between
RHD
cases
and
normal
controls
in
Uganda
.
One
hundred
ninety-
nine
participants
including
96
established
RHD
cases
aged
5
-
60
years
and
103
age
and
sex
matched
normal
controls
were
recruited
for
participation
.
DNA
was
manually
extracted
from
buffy
coat
samples
and
HLA
analysis
was
performed
.
HLA-
DR
allelic
frequency
comparison
between
cases
and
controls
were
estimated
using
conditional
logistic
regression
with
95
%
confidence
intervals
.
P
-
values
were
corrected
for
multiple
hypothesis
testing
.
199
participants
(
103
female
,
51
.
8
%
)
completed
the
study
.
The
mean
(
SD
)
age
in
years
for
cases
and
controls
were
29
.
6
(
10
.
2
)
and
29
(
18
)
,
respectively
.
After
conditional
logistic
regression
and
multiple
hypothesis
testing
,
HLA-
DR
1
was
associated
with
a
decreased
risk
of
RHD
(
OR
=
0
.
42
,
CI
0
.
21
-
085
,
P
=
0
.
01
,
Corrected
P
value
(
PC
)
 
=
0
.
09
,
)
while
HLA-
DR
1
1
was
associated
with
increased
risk
of
RHD
(
OR
=
3
.
31
,
CI
1
.
57
-
6
.
97
,
P
=
 
<
0
.
001
,
Pc
<
0
.
001
)
.
No
other
significant
associations
were
found
.
In
this
first
study
of
HLA
genetic
susceptibility
to
RHD
in
Uganda
,
HLA-
DR
1
was
more
common
in
normal
controls
while
HLA-
DR
1
1
was
more
common
among
RHD
cases
suggesting
a
disease
susceptibility
association
.
In
future
studies
,
high
resolution
HLA
analysis
and
genome
wide
studies
should
be
carried
out
to
confirm
this
pattern
.
Diseases
Validation
Diseases presenting
"susceptibility association"
symptom
acute rheumatic fever
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