|
Gene
|
SNP
|
Ancestral Allel
|
Genotypes
|
Total, n
|
MTX intolerant1
|
MTX tolerant
|
p-value
|
MTX Nausea2
|
Controls
|
p-value
|
|---|
|
ABCC2
|
rs2273697
|
G
|
GG
|
74
|
44
|
29
|
χ2 = 0.05
|
32
|
14
|
0.81
|
|
GA
|
32
|
20
|
12
|
p = 0.98
|
16
|
5
|
|
AA
|
13
|
8
|
5
| |
8
|
2
|
|
ABCC2
|
rs37400663
|
G
|
GG
|
38
|
23
|
15
|
0.74
|
19
|
7
|
1.00
|
|
GA
|
65
|
38
|
27
| |
29
|
12
|
|
AA
|
15
|
10
|
4
| |
7
|
2
|
|
ABCC2
|
rs717620
|
G
|
GG
|
73
|
47
|
26
|
0.64
|
35
|
13
|
1.00
|
|
GA
|
39
|
21
|
17
| |
18
|
7
|
|
AA
|
7
|
4
|
3
| |
3
|
1
|
|
ABCB1
|
rs2032582
|
G
|
GG
|
38
|
23
|
15
|
0.28
|
18
|
6
|
0.95
|
|
GT
|
58
|
34
|
24
| |
27
|
10
|
|
GA
|
2
|
0
|
2
| |
1
|
1
|
|
TA
|
3
|
3
|
0
| |
2
|
1
|
|
TT
|
18
|
12
|
5
| |
8
|
3
|
|
ABCB1
|
rs1045642
|
C
|
CC
|
18
|
9
|
9
|
χ2 = 1.34
|
8
|
4
|
0.82
|
|
CT
|
68
|
44
|
24
|
p = 0.51
|
34
|
11
|
|
TT
|
33
|
19
|
13
| |
14
|
6
|
|
SLCO1B1
|
rs4149056
|
T
|
TT
|
84
|
49
|
34
|
0.86
|
39
|
15
|
1.00
|
|
TC
|
32
|
21
|
11
| |
16
|
6
|
|
CC
|
3
|
2
|
1
| |
1
|
0
|
|
SLCO1B1
|
rs4149081
|
G
|
GG
|
80
|
47
|
32
|
0.86
|
38
|
14
|
1.00
|
|
GA
|
36
|
23
|
13
| |
17
|
7
|
|
AA
|
3
|
2
|
1
| |
1
|
0
|
|
SLCO1B3
|
rs2117032
|
C
|
CC
|
17
|
12
|
5
|
χ2 = 2.16
|
10
|
4
|
0.63
|
|
CT
|
53
|
28
|
24
|
p = 0.34
|
23
|
6
|
|
TT
|
49
|
32
|
17
| |
23
|
11
|
|
SLC19A1
|
rs10512663
|
G
|
GG
|
33
|
18
|
15
|
χ2 = 0.76
|
17
|
6
|
0.89
|
|
GA
|
66
|
42
|
24
|
p = 0.68
|
28
|
12
|
|
AA
|
19
|
11
|
7
| |
10
|
3
|
|
HTR3A
|
rs1062613
|
C
|
CC
|
80
|
52
|
28
|
0.13
|
36
|
16
|
0.58
|
|
CT
|
37
|
20
|
16
| |
19
|
5
|
|
TT
|
2
|
0
|
2
| |
1
|
0
|
|
HTR3A
|
rs1985242
|
A
|
AA
|
7
|
3
|
4
|
0.23
|
4
|
1
|
0.34
|
|
AT
|
55
|
30
|
24
| |
28
|
7
|
|
TT
|
57
|
39
|
18
| |
24
|
13
|
|
HTR3A
|
rs1176713
|
C
|
CC
|
6
|
3
|
3
|
0.68
|
3
|
1
|
0.18
|
|
CT
|
37
|
21
|
16
| |
19
|
3
|
|
TT
|
76
|
48
|
27
| |
34
|
17
|
|
HTR3B
|
rs1776744
|
T
|
TT
|
50
|
30
|
20
|
0.09
|
24
|
10
|
0.58
|
|
TG
|
58
|
32
|
25
| |
27
|
8
|
|
GG
|
11
|
10
|
1
| |
5
|
3
|
|
MTHFR
|
rs18011313
|
A
|
AA
|
52
|
34
|
18
|
χ2 = 0.93
|
24
|
9
|
0.29
|
|
AC
|
53
|
30
|
22
|
p = 0.63
|
21
|
11
|
|
CC
|
13
|
7
|
6
| |
10
|
1
|
|
MTHFR
|
rs1801133
|
C
|
CC
|
58
|
33
|
25
|
0.02
|
27
|
10
|
1.00
|
|
CT
|
51
|
29
|
21
| |
24
|
10
|
|
TT
|
10
|
10
|
0
| |
5
|
1
|
- The genotype distribution for the selected single nucleotide polymorphisms (SNPs) – including the distribution of genotypes within the phenotype subgroups defined by the methotrexate intolerance severity score and the nausea diary
- SNP; Single Nucleotide Polymorphism
- 1The MTXintolerant subgroup: children with a total score of the Methotrexate Intolerance Severity Score (MISS) ≥6 and at least 1 point in the anticipatory and/or associative and/or behavioral symptoms (n = 72). Otherwise categorised as MTXtolerant (n = 46)
- 2The “MTX-nausea” subgroup: children with a nausea diary illustrating a nausea pattern timely related to the MTX administration (n = 56). The remaining children grouped as “Controls” (n = 21)
- 3SNP variant not available for one child
