Supplementary Tables:

Table 1. Stratification analysis of confounding factors on association between CCL2-2518A/G, CXCL10-201A/G and IL-8+781C/T and disease severity in EV-71 infected cases.

CCL2-2518A/G
genotype / Mild cases
n=103 / Severe cases
n=83 /
P / OR (95%CI)
Male, n (%) / AA
AG
GG
G allele / 8 (15.7)
38 (74.5)
5 (9.8)
43 (84.3) / 4 (6.2)
24 (37.5)
36 (56.3)
60 (93.8) / <0.001
0.111 / 5.33 (2.47-11.49)
2.79 (0.79-9.86)
Female, n (%) / AA
AG
GG
G allele / 8 (15.4)
21 (40.4)
23 (44.2)
44 (84.6) / 0 (0)
10 (52.6)
9 (47.4)
19 (100) / 0.306
0.003 / 1.54 (0.67-3.53)
0.16 (0.51-0.53)
Age≤3 y, n (%) / AA
AG
GG
G allele / 10 (26.3)
24 (63.2)
4 (10.5)
28 (73.7) / 3 (4.4)
29 (42.7)
36 (52.9)
65 (95.6) / <0.001
0.003 / 5.83 (2.58-13.15)
7.74 (1.98-30.28)
Age>3 y, n (%) / AA
AG
GG
G allele / 6 (9.2)
35 (53.9)
24 (36.9)
59 (90.8) / 1 (6.7)
5 (33.3)
9 (60.0)
14 (93.3) / 0.185
0.676 / 1.96 (0.73-5.31)
1.53 (0.21-11.06)
CXCL10-201A/G
Genotype
Male, n (%) / AA
AG
GG
A allele / 0 (0)
7 (13.7)
44 (86.3)
7 (13.7) / 2 (3.1)
13 (20.3)
49 (76.6)
15 (23.4) / 0.134
0.193 / 2.00 (0.81-4.98)
1.92 (0.72-5.15)
Female, n (%) / AA
AG
GG
A allele / 0 (0)
4 (7.7)
48 (92.3)
4 (7.7) / 1 (5.4)
9 (47.4)
9 (47.4)
10 (52.6) / <0.001
<0.001 / 0.08 (0.02-0.31)
0.08 (0.02-0.29)
Age≤3 y, n (%) / AA
AG
GG
A allele / 0 (0)
5 (13.2)
33 (86.8)
5 (13.2) / 2 (2.9)
18 (26.5)
48 (70.6)
20 (29.4) / 0.055
0.060 / 2.73 (0.98-7.62)
2.74 (0.96-7.83)
Age>3 y, n (%) / AA
AG
GG
A allele / 0 (0)
6 (9.2)
59 (90.8)
6 (9.2) / 1 (6.7)
4 (26.7)
10 (66.6)
5 (33.4) / 0.015
0.022 / 4.79 (1.36-16.88)
4.92 (1.26-19.21)
IL8 +781C/T
Genotype
Male, n (%) / CC
CT
TT
C allele / 8 (15.7)
33 (64.7)
10 (19.6)
41 (80.4) / 37 (57.8)
25 (39.1)
2 (3.1)
62 (96.9) / <0.001
0.026 / 5.38 (2.55-11.36)
4.60 (1.20-17.56)
Female, n (%) / CC
CT
TT
C allele / 18 (34.6)
29 (55.8)
5 (9.6)
47 (90.4) / 10 (52.6)
8 (42.1)
1 (5.3)
18 (94.7) / 0.223
0.506 / 1.77 (0.71-4.44)
1.97 (0.27-14.52)
Age≤3 y, n (%) / CC
CT
TT
C allele / 10 (26.3)
21 (55.3)
7 (18.4)
31 (81.6) / 37 (54.5)
29 (42.6)
2 (2.9)
66 (97.1) / 0.001
0.018 / 3.16 (1.57-6.36)
6.80 (1.39-33.33)
Age>3 y, n (%) / CC
CT
TT
C allele / 16 (24.6)
41 (63.1)
8 (12.3)
57 (87.7) / 10 (66.7)
4 (26.6)
1 (6.7)
14 (93.3) / 0.011
0.504 / 4.07 (1.39-11.93)
1.99 (0.26-15.03)

The associations were performed by logistic regression analysis adjusted with covariates (including gender and age).

Table 2. Effects of CCL2, CXCL10 and IL8 gene polymorphisms on EV71 infection

Gene/ Items / Gender
(Male/
Female) / Age
(years) / Fever (days) / WBC
(×109/L) / CRP
(mg/L) / BG
(mmol/L) / ALT
(U/L) / AST
(U/L) / CK-MB
(U/L)
CCL2 -2518A/G
Genotype
AA
AG
GG
P / 12/8
62/31
41/32
0.379 / 2.9±1.1
3.1±1.2
3.1±1.2
0.714 / 2.1
(1.1-2.9)
2.5
(1.5-3.5)
3.0
(2.0-4.0)
0.022 / 5.9
(4.7-8.9)
8.5
(6.1-13.1)
12.9
(7.4-14.4)
<0.001 / 5.5±2.7
7.1±2.7
8.2±2.4
<0.001 / 5.7
(5.2-8.2)
6.9
(5.7-11.8)
10.0
(6.5-11.3)
0.006 / 17.5
(15.0-22.0)
20.0
(15.0-25.0)
18.0
(15.0-24.5)
0.393 / 22.0
(20.0-29.0)
26.0
(20.5-37.0)
24.0
(20.0-33.5)
0.265 / 14.0
(7.3-23.0)
15.0
(10.0-19.5)
14.0
(9.5-21.0)
0.925
Carriage frequency
G
non G
P / 103/63
12/8
0.859 / 2.9
(2.1-3.9)
2.8
(2.2-3.3)
0.523 / 2.5
(2.0-3.5)
2.1
(1.1-2.9)
0.029 / 9.5
(6.8-13.8)
5.9
(4.7-8.9)
0.001 / 7.6±2.7
5.5±2.7
0.001 / 8.2
(5.9-11.3)
5.7
(5.2-8.2)
0.010 / 19.0
(15.0-25.0)
17.5
(15.0-22.0)
0.260 / 25
(20.0-37.0)
22.0
(20.0-29.0)
0.210 / 15.0
(10.0-20.3)
14.0
(7.3-23.0)
0.695
CXCL10
-201A/G Genotype
AA
AG
GG
P / 2/1
20/13
93/57
0.974 / 2.6±0.7
2.7±0.9
3.2±1.2
0.066 / 4.0
(3.0-5.0)
3.0
(2.0-4.3)
2.0
(1.5-3.5)
0.052 / 15.2
(13.2-7.1)
12.3
(7.3-13.8)
8.5
(5.9-13.8)
0.041 / 11.7±1.3
8.2±2.8
7.1±2.7
0.002 / 13.1±1.7
(11.3--14.6)
10.2
(5.9-12.1)
7.1
(5.7-10.7)
0.011 / 17.0
(12.0-43)
18.0
(16.0-24.0)
19.0
(15.0-25.0)
0.971 / 21.0
(20.0-40.0)
22.0
(20.0-36.5)
25.0
(20.0-34.3)
0.760 / 14.0
(9.0-24.0)
15.0
(8.5-23.5)
14.0
(10.0-19.0)
0.823
Carriage frequency
A
non A
P / 22/14
93/57
0.921 / 2.7±0.9
3.2±1.2
0.020 / 3.0
(2.0-4.4)
2.0
(1.5-3.5)
0.037 / 12.5
(7.5-13.9)
8.5
(5.9-13.8)
0.065 / 8.5±2.9
7.1±2.7
0.007 / 10.8
(6.0-12.4)
7.1
(5.7-10.7)
0.012 / 17.5
(16.0-24.5)
19.0
(15.0-25.0)
0.867 / 22.0
(20.0-36.8)
25.0
(20.0-34.3)
0.461 / 15.0
(9.0-23.8)
14.0
(10.0-19.0)
0.538
IL8
+781C/T
Genotype
CC
CT
TT
P / 45/28
58/37
12/6
0.903 / 2.8±1.0
3.2±1.3
3.3±1.2
0.073 / 3.0
(2.0-4.0)
2.0
(1.5-3.0)
2.0
(2.0-3.1)
0.017 / 13.1
(7.0-14.2)
8.3
(5.8-12.9)
7.7
(7.1-9.1)
0.010 / 9.1
(5.8-10.1)
6.8
(5.1-9.1)
5.2
(3.5-6.6)
<0.001 / 11.3
(6.5-13.1)
6.8
(5.7-10.2)
6.1
(5.7-6.9)
<0.001 / 19.0
(17.0-25.5)
18.0
(15.0-25.0)
18.5
(15.0-22.3)
0.411 / 27.0
(20.0-27.5)
25.0
(20.0-33.0)
24.5
(20.8-30.8)
0.778 / 16.0
(9.0-23.5)
14.0
(10.0-19.0)
14.0
(9.0-19.5)
0.358
Carriage frequency
C
non C
P / 103/65
12/6
0.257 / 2.9
(2.1-3.9)
3.1
(2.3-4.7)
0.283 / 2.5
(1.6-3.5)
2.0
(2.0-3.1)
0.769 / 9.4
(6.0-13.8)
7.7
(7.1-9.1)
0.353 / 8.2
(5.4-9.6)
5.2
(3.5-6.8)
<0.001 / 8.3
(5.8-11.8)
6.1
(5.7-6.9)
0.006 / 18.5
(15.0-25.0)
18.5
(15.0-23.3)
0.906 / 25.0
(20.0-36.8)
24.5
(20.7-30.8)
0.778 / 15.0
(9.3-20.8)
14.0
(9.0-19.5)
0.505

A total of 186 EV71-infected patients were included in the study. WBC, white blood cell counts; CRP, C-reactive protein; BG, blood glucose; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK-MB, creatine kinase-myocardial isozyme.

Table 3. Comparison of CCL2, CXCL10 and IL8 gene polymorphisms in CSF evaluations

Gene/ Items / CSF
Glucose
(mmol/L) / Chloride
(mmol/L) / Protein
(mg/L) / Cell counts
(×106) / Lymphocyte
(×106) / Monocyte
(%)
CCL2 -2518A/G
Genotype
AA
AG
GG
P / 3.0
4.0
(3.0-4.0)
4.0
(3.0-4.0)
0.582 / 120.5
120.6
(118.4-124.2)
119.0
(117.1-122.3)
0.243 / 203.0
206.0
(140.0-231.5)
222.0
(178.0-249.0)
0.555 / 80.0
14.5
(7.8-40.5)
20.0
(8.0-92.0)
0.560 / 60.0
19.1±23.0
20.3±22.0
0.221 / 18.0
20.3±5.1
17.3±4.4
0.183
Carriage frequency
G
non G
P / 4.0
(3.0-4.0)
3.0
0.526 / 120.2
(118.0-122.8)
120.5
0.895 / 209.0
(176.5-243.5)
203.0
0.789 / 15
(8.0-48.0)
80.0
0.747 / 8.0
(4.0-21.0)
60.0
0.211 / 18.4±4.8
18.0
0.930
CXCL10
-201A/G Genotype
AA
AG
GG
P / 3.0±0.0
3.4±1.0
3.5±1.7
0.914 / 124.0
(120.5-127.5)
120.4
(118.2-123.3)
119.4
(117.2-122.2)
0.305 / 159.0±62.2
213.9±63.9
241.1±121.1
0.455 / 43.0
(6.0-80.0)
23.5
(9.3-48.0)
13.0
(8.0-80.5)
0.790 / 32.0±39.6
23.5±26.3
17.8±18.7
0.598 / 19.0±1.4
19.9±5.4
17.2±4.2
0.247
Carriage frequency
A
non A
P / 3.4±1.0
3.5±1.7
0.896 / 120.5
(118.3-123.7)
119.4
(117.2-122.2)
0.251 / 207.8±64.4
241.1±121.1
0.306 / 23.5
(8.0-56.0)
13.0
(8.0-80.5)
0.613 / 24.4±26.6
17.8±18.7
0.372 / 19.8±5.1
17.2±4.2
0.096
IL8
+781C/T
Genotype
CC
CT
TT
P / 4.0
(3.0-4.0)
4.0
(3.0-4.0)
7.0
0.062 / 120.5
(118.3-123.6)
119.2
(117.5-122.5)
117.1
0.221 / 207.7±79.2
254.0±124.9
228.0
0.394 / 22.0
(11.0-80.0)
10.5
(6.0-62.0)
42.0
0.259 / 22.8±24.7
17.9±20.5
20.0
0.827 / 19.4±4.7
17.1±4.8
15.0
0.279
Carriage frequency
C
non C
P / 4.0
(3.0-4.0)
7.0
0.053 / 120.3
(118.1-122.8)
117.1
0.316 / 207.0
(176.5-243.5)
228.0
0.684 / 15.0
(8.0-64.0)
42.0
0.684 / 8.0
(4.0-24.5)
20.0
0.842 / 18.4±4.8
15.0
0.474

A total of 38 EV71encephalitis patients were included in the study. CSF, cerebrospinal fluid.