Saribas S, Demiryas S, Yilmaz E, Uysal O, Kepil N, Demirci M, Caliskan R, Dinc HO, Akkus S, Gareayaghi N, Kirmusaoglu S, Ozbey D, Tokman HB, Koksal SS, Tasci I, Kocazeybek B. Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders. World J Gastroenterol 2020; 26(32): 4817-4832 [PMID: 32921959 DOI: 10.3748/wjg.v26.i32.4817]
Corresponding Author of This Article
Bekir Kocazeybek, PhD, Full Professor, Professor, Department of Medical Microbiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Cerrahpasa Street, Istanbul 34098, Turkey. bzeybek@istanbul.edu.tr
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Control Study
Open-Access Policy of This Article
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Table 2 Comparison of human leukocyte antigen alleles predisposing susceptibility and resistance to gastric cancer/duodenal ulcer in patient and control groups, n (%)
HLA alleles
Patient groupGC + DU, H. pylori (+) (n = 94, alleles = 198)
Control groupNUD + Asymptomatic, H. pylori (+) (n = 86, alleles = 172)
OR
95%CI
P value
Minimum
Maximum
HLAs increasing susceptibility to GC/DU
HLA-A*02
52 (27.6)
38 (22)
1.34
0.833
2.182
0.2239
HLA-B*35
40 (21.3)
26 (15.1)
1.51
0.880
2.615
0.1329
HLA-DRB1*13
36 (19)
24 (14)
1.46
0.831
2.567
0.1880
HLA-DQA1*01
76 (40)
30 (17.4)
3.21
1.968
5.242
0.0001
HLA-DQB1*06
52 (27.6)
20 (11.6)
2.90
1.652
5.139
0.0002
HLAs making resistant to GC/DU
HLA-A*03
14 (7.4)
20 (11.6)
0.61
0.298
1.252
0.1787
HLA-B*50
0 (0)
10 (5.8)
0.08
0.010
0.680
0.0201
HLA-DRB1*04
16 (8.5)
24 (14)
0.57
0.293
1.120
0.1038
HLA-DQA1*05
28 (14.9)
54 (31.4)
0.38
0.228
0.639
0.0003
HLA-DQB1*03
42 (23)
64 (37.2)
0.48
0.305
0.770
0.0022
Table 3 The comparison of human leukocyte antigen alleles which increase or decrease the gastric cancer risk in gastric cancer subgroup cases in terms of CagA+ (≥ 2) EPIYA-C, n (%)
GC (≥ 2) EPIYA-C (n = 26, alleles = 52)
GC (< 2) EPIYA-C (n = 18, alleles = 36)
OR
95%CI
P value
Minimum
Maximum
HLA-A*02
12 (23)
10 (27)
0.78
0.29
2.06
0.6170
HLA-B*35
12 (23)
10 (27)
0.78
0.29
2.06
0.6170
HLA-DRB1*13
12 (23)
12 (33)
0.60
0.23
1.54
0.2903
HLA-DQA1*01
24 (46)
16 (44)
1.07
0.45
2.51
0.8742
HLA-DQB1*06
12 (23)
16 (44)
0.37
1.14
2.90
0.0369
Table 4 The comparison of human leukocyte antigen alleles which increase or decrease the duodenal ulcer risk in duodenal ulcer subgroup in terms of CagA+(≥ 2) EPIYA-C, n (%)
DU (≥ 2) EPIYA-C (n = 14, alleles = 28)
DU (< 2) EPIYA-C (n = 36, alleles = 72)
ORc
95%CI
P value
Minimum
Maximum
HLA-A*02
10 (36)
20 (27)
1.44
0.53
3.62
0.4380
HLA-B*35
4 (14)
14 (19)
0.80
0.24
0.680
0.0201
HLA-DRB1*13
6 (21)
6 (8)
3
0.87
10.26
0.0801
HLA-DQA1*01
10 (36)
26 (36)
0.9
0.39
2.44
0.9704
HLA-DQB1*06
8 (28)
16 (22)
1.4
0.52
3.75
0.5340
Table 5 The comparison of human leukocyte antigen alleles which increase or decrease the gastric cancer/duodenal ulcer risk in gastric cancer and duodenal ulcer subgroups in terms of CagA+(≥ 2) EPIYA-C, n (%)
GC(≥ 2) EPIYA-C (n = 26, alleles=52)
DU(≥ 2) EPIYA-C (n = 14, alleles=28)
OR
95%CI
P value
Minimum
Maximum
HLA-A*02
12 (23)
10 (36)
0.54
0.19
1.47
0.2302
HLA-B*35
12 (23)
4 (14)
1.80
0.52
6.21
0.3527
HLA-DRB1*13
12 (23)
6 (21)
1.10
0.36
3.83
0.8663
HLA-DQA1*01
24 (46)
10 (36)
1.54
0.59
3.97
0.3689
HLA-DRB1*06
12 (23)
8 (28)
0.75
0.26
2.12
0.5889
Table 6 Results of logistic regressions analysis according to the variables in patient group (gastric cancer and duodenal ulcer cases)
P value
OR
95%CI
Lower
Upper
HLA-DQA1*01
0.004
1.848
1.215
2.811
HLA-DQA1*05
0.050
HLA-DQB1*03
0.061
HLA-DQB1*06
0.009
1.821
1.163
2.850
HLA-A*02
0.040
1.579
1.021
2.442
HLA-A*25
0.999
Table 7 Frequency of detected human leukocyte antigen class I alleles and the class II alleles in patients with cancer and ulcer and in the control groups, n (%)
HLA-A
Allele frequency
HLA-B
Allele frequency
HLA-DRB1
Allele frequency
HLA-DQA1
Allele frequency
HLA-DQB1
Allele frequency
Alleles
Cases (n = 94)
Control (n = 86)
Alleles
Cases (n = 94)
Control (n = 86)
Alleles
Cases (n = 94)
Control (n = 86)
Alleles
Cases (n = 94)
Control (n = 86)
Alleles
Cases (n = 94)
Control (n = 86)
01
22 (11.4)
24 (13.9)
07
18 (9.5)
22 (12.8)
01
14 (7.4)
8 (4.6)
01
76 (40)
30 (17.4)
02
20 (10.6)
26 (15.1)
02
52 (27.6)
38 (22)
08
6 (3.2)
6 (3.5)
03
10 (5.3)
10 (5.8)
02
20 (10.6)
20 (11.6)
03
42 (23)
64 (37.2)
03
14 (7.4)
20 (11.6)
13
6 (3.2)
4 (2.3)
04
16 (8.5)
22 (12.7)
03
12 (6.4)
22 (12.8)
04
26 (13.8)
28 (16.2)
11
18 (9.5)
18 (10.4)
14
6 (3.2)
4 (2.3)
07
10 (5.3)
20 (11.6)
04
16 (8.5)
20 (11.6)
05
48 (25.5)
34 (19.8)
23
10 (5.3)
4 (2.3)
15
2 (1)
6 (3.5)
08
4 (2.1)
6 (3.5)
05
28 (14.9)
54 (31.4)
06
52 (27.6)
20 (11.6)
24
26 (13.8)
24 (13.9)
18
10 (5.3)
10 (5.8)
10
6 (3.2)
4 (2.3)
06
36 (19.1)
26 (15.1)
25
0 (0)
2 (1.1)
27
6 (3.2)
4 (2.3)
11
34 (18)
42 (24.4)
26
4 (2.1)
4 (2.3)
35
40 (21.3)
26 (15.1)
12
6 (3.2)
2 (1.2)
29
8 (4.2)
8 (4.6)
37
4 (2.1)
0 (0)
13
36 (19)
24 (14)
30
4 (2.1)
6 (3.4)
38
8 (4.2)
2 (1.2)
14
18 (9.5)
8 (4.6)
31
2 (1)
4 (2.3)
39
0 (0)
4 (2.3)
15
28 (14.9)
22 (12.8)
32
16 (8.5)
10 (5.8)
40
6 (3.2)
6 (3.5)
16
6 (3.2)
4 (2.3)
33
6 (3.1)
4 (2.3)
41
4 (2.1)
2 (1.2)
68
4 (2.1)
6 (3.4)
44
8 (4.2)
14 (8.1)
69
2 (1)
0 (0)
45
0 (0)
2 (1.2)
48
2 (1)
2 (1.2)
49
6 (3.2)
4 (2.3)
50
0 (0)
10 (5.8)
51
24 (12)
30 (17.4)
52
14 (7.4)
2 (1.2)
53
0 (0)
2 (1.2)
54
2 (1)
0 (0)
55
6 (3.2)
8 (4.6)
57
2 (1)
2 (1.2)
58
8 (4.2)
0 (0)
78
0 (0)
0 (0)
Table 8 The distribution of EPIYA motifs for study and control groups, n (%)
EPIYA-C repeat patterns
Patient group
Control group
Total (n = 140)
Gastric cancer
Duodenal ulcer
Non-ulcer dyspepsia
Individuals with normal gastrointestinal system
ABC
12
(27.2)
34
(68)
28
(93.3)
16
(100)
90
AC
2
(4.5)
2
(4)
-
-
4
BC
2
(4.5)
-
-
-
2
ABCC
16
(36.4)
8
(16)
-
-
24
BCC
2
(4.6)
2
(4)
2
(6.7)
-
6
ACCC
-
-
-
-
-
ABCC
8
(18.2)
4
(8)
-
-
12
AB
2
(4.6)
-
-
-
2
Total
44
(100)
50
(100)
30
(100)
16
(100)
140
Citation: Saribas S, Demiryas S, Yilmaz E, Uysal O, Kepil N, Demirci M, Caliskan R, Dinc HO, Akkus S, Gareayaghi N, Kirmusaoglu S, Ozbey D, Tokman HB, Koksal SS, Tasci I, Kocazeybek B. Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders. World J Gastroenterol 2020; 26(32): 4817-4832