SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
VOLUME 7 NUMBER 4 • NOVEMBER 2010
151
p
=
1.2
×
10
-3
, 3.66,
p
=
4,2
×
10
-4
respectively, and for the LADA
group, OR
=
5.09;
p
=
2.8
×
10
-8
, 3.08;
p
=
1.0
×
10
-4
, 4.64;
p
=
2.3
×
10
-7
, 3.79,
p
=
1.2
×
10
-5
, respectively.
The frequency of HLA-DR5, -DR15 and -DQ6 were reduced in
the diabetic patients with regard to the control population and
therefore appeared to be protective for T1D in children (OR
=
0.03,
p
=
1.6
×
10
-8
; 0.0,
p
=
4.1
×
10
-6
and 0.0,
p
=
2.3
×
10
-9
), juveniles
(OR
=
0.21,
p
=
4.5
×
10
-3
; 0.26,
p
=
0.046 and 0.63,
p
=
0.2) and
LADA group (OR
=
0.27,
p
=
2.3
×
10
-4
; 0.31,
p
=
7.4
×
10
-3
and
0.29,
p
=
5.2
×
10
-4
).
Comparison of the frequencies of DR-DQ markers HLA
class II among the patients
Table 3 illustrates the frequency of the HLA class II DR-DQ antigen
combinations. The HLA-DR3/DQ2 and -DR4/DQ8 (Q3) were
significantly positively associated with type 1 diabetes in all three
case groups (children, juveniles and LADA) in the Algerian cohort.
The calculation of OR showed that of the three categories of
patients, the highest risk was observed with the -DR3/DQ2 in the
children (OR
=
12.4), with values of 8.34 and 10.12 for the juvenile
and LADA groups, respectively. The OR values associated with the
DR4/DQ8 (3) for the juvenile and LADA groups were 6.2 and 6.34,
respectively. The group of children also had the highest value of the
three groups for the DR4/DQ8; OR
=
12.84.
Comparison of the frequencies of the homozygotes
and heterozygotes among patients
In our study, we compared frequencies among the 210 diabetics
(Table 4) for the presence of antigens HLA-DR4 and HLA-DR3, i.e.
DR3/DR4, with respective values of 37.65, 15.56 and 22.50%;
DR3/DRX, with frequencies of 17.65, 28.89 and 30%; and finally
DR4/DRX, with frequencies of 15.29, 24.44 and 17.50%. However,
the frequency of homozygotes DR3/DR3 and DR4/DR4 were 17.65
and 11.76% respectively in the children, 22.22 and 6.67% for the
juveniles, and 17.5 and 11.25% for the LADA. The calculation of
OR showed that the highest value was observed in the children and
LADA groups, with respective values of the DR3/DR4 combination
of 8.8 and 4.23. For the juveniles, we observed that the risk was
higher for the DR3/DRX combination, with an OR value of 2.94.
The results indicate that the highest risk associated with diabetes
was the presence of the HLA-DR3/DR4 combination. Our results
also show that the disease was most frequent in children with the
DR3/DR4 antigen combination (37.65 vs 6.43% in controls,
p
=
7.3
×
10
-9
, OR
=
8.8). In the juvenile group T1D was most strongly
associated with the presence of the HLA-DR3/DRX combination
(28.89 vs 12.14%,
p
=
9.9
×
10
-3
, OR
=
2.94). In the LADA group,
the incidence of T1D was highest with the DR3/DRX-positive
individuals (30 vs 12.14%,
p
= 1.2
×
10
-3
, OR
=
3.1).
The comparison of the frequency of the marker of protection
Table 2.
The odds ratios and
p
-values for the statistically significant HLA class II antigens for the three diabetic sub-groups.
Subjects
Children
Juveniles
LADA
Markers DR/DQ OR
χ
2
ε
p
OR
χ
2
ε
p
OR
χ
2
ε
p
DR3
DR4
DQ2
DQ8
DR5
DR15 (2)
DQ6 (1)
5.54
5.1
5.02
7.67
0.03
0.21
0.27
32.56
30.5
27.9
45.1
25.757
6.149
11.46
5.71
5.44
5.32
6.51
2.39
3.55
3.2
×
10
-9
1.5
×
10
-8
3.7
×
10
-8
7.7
×
10
-12
1.6
×
10
-8
4.5
×
10
-3
2.3
×
10
-4
4.36
2.66
3.09
3.66
0.0
0.26
0.31
16.18
6.9
9.2
16.96
14.25
2.58
5.5
4.89
3.28
3.88
4.12
1.87
2.53
3.2
×
10
-5
4.9
×
10
-3
1.2
×
10
-3
4.2
×
10
-4
4.1
×
10
-6
0.046
7.4
×
10
-3
5.09
3.08
4.64
3.79
0.0
0.63
0.29
30.54
15.03
26.02
19.46
27.08
1.11
11.11
5.46
3.77
5.1
4.23
1.05
3.33
2.8
×
10
-8
1.0
×
10
-4
2.3
×
10
-7
1.2
×
10
-5
2.3
×
10
-9
0.2
5.2
×
10
-4
Table 3.
Frequency of combinations of HLA-DR/DQ antigens among type 1 diabetes and controls
Subjects
Children (
n
=
85)
Juveniles (
n
=
45)
LADA (
n
=
80)
Controls
(
n
=
140) (%)
Markers
n
(%)
OR
p
n
(%)
OR
p
n
(%)
OR
p
DR3/DQ2
DR4/DQ8 (3)
62 (72.94)
53 (62.35)
12.4
12.84
1.1
×
10
-16
1.2
×
10
-15
29 (64.44)
20 (44.44)
8.76
6.2
5.4
×
10
-9
5.6
×
10
-6
55 (68.75)
36 (45)
10.12
6.34
5.1
×
10
-14
3.2
×
10
-8
25 (17.86)
16 (11.43)
Table 4.
Comparison of the frequencies of the homozygotes and heterozygotes among patients and controls
Subjects
Children (
n
=
85)
Juveniles (
n
=
45)
LADA (
n
=
80)
Controls
(
n
=
140) (%)
Markers
n
(%)
OR
p
n
(%)
OR
p
n
(%)
OR
p
DR3/DR3
DR4/DR4
DR3/DRX
DR4/DRX
DR3/DR4
15 (17.65)
10 (11.76)
15 (17.65)
13 (15.29)
32 (37.65)
–
–
1.55
0.97
8.8
2.0
×
10
-7
4.2
×
10
-5
ns
ns
7.3
×
10
-9
10 (22.22)
3 (6.67)
13 (28.89)
11 (24.44)
7 (15.56)
–
–
2.94
1.74
2.68
2.0
×
10
-7
0.014
9.9
×
10
-3
ns
ns
14 (17.5)
9 (11.25)
24 (30)
14 (17.5)
18 (22,5)
–
–
3.1
1.14
4.23
3.2
×
10
-7
8.2
×
10
-9
1.2
×
10
-3
ns
6.5
×
10
-4
0 (0.0)
0 (0.0)
17 (12.14)
22 (15.71)
9 (6.43)
Only the most frequent genotypes in the DR3/X and DR4/X group are shown, X being non-R3 or/non-DR4; ns: not significant.
