1Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan.
2Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Japan.
3Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
4Department of Inflammatory Bowel Disease Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
© Copyright 2017. Korean Association for the Study of Intestinal Diseases.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Financial support: This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (grant number: 15K08976) and the Program for Promoting Practical Applications of Genomic Medicine of the Japan Agency for Medical Research and Development (AMED).
Conflict of interest: None.
Variable | Total | No leukopenia | Leukopenia | P-valuea |
---|---|---|---|---|
Sex (male/female) | 96/64 | 60/41 (59.4/40.6) | 36/23 (61.0/39.0) | 0.8686 |
Age (yr) | 40.3 (18–74) | 38.3 (18–74) | 43.6 (20–74) | 0.0069 |
Body weight (kg) | 54.6 (37–90) | 53.7 (31–80) | 54.4 (38–77) | 0.6358 |
Diagnosis | 0.2706 | |||
CD | 86 | 57 (66.3) | 29 (33.7) | |
UC | 72 | 44 (61.1) | 28 (38.9) | |
IBDu | 1 | 0 | 1 (100.0) | |
Intestinal Behçet | 1 | 0 | 1 (100.0) | |
5-ASA | 0151 | 98 (64.9) | 53 (35.1) | 0.0767 |
Prednisolone | 94 | 59 (62.8) | 35 (37.2) | 0.9106 |
Anti-TNF-α agent (infliximab or adalimumab) | 89 | 62 (69.7) | 27 (30.3) | 0.0697 |
AZA/6-MP | 123/37 | 84/17 (83.2/16.8) | 39/20 (66.1/33.9) | 0.0135 |
Initial AZA dose (mg/kg/day) | 0.759±0.247 | 0.757±0.229 | 0.764±0.287 | 0.5760 |
Initial 6-MP dose (mg/kg/day) | 0.316±0.167 | 0.282±0.098 | 0.331±0.196 | 0.9680 |
Follow-up period of thiopurine therapy (mo) | 43.6 (0.25–132.00) | 42.1 (0.25–132.00) | 46.0 (0.50–126.00) | 0.9965 |
Values are presented as number (%), mean (range), or mean±SD.
aNo leukopenia vs. leukopenia.
IBDu, IBD unclassified; 5-ASA, 5-aminosalicylic acid; TNF-α, tumor necrosis factor α; AZA, azathioprine; 6-MP, 6-mercaptopurine.
Genotype | Total (n=160) | CD (n=86) | UC (n=72) | IBDu (n=1) | Intestinal Behçet (n=1) |
---|---|---|---|---|---|
NUDT15 p.Val18_Val19insGlyVal | |||||
-/- | 149 (93.1) | 80 (53.7) | 67 (45.0) | 1 (0.7) | 1 (0.7) |
-/GGAGTC | 11 (6.9) | 6 (54.5) | 5 (45.5) | 0 | 0 |
NUDT15 p.Val18Ile | |||||
G/G | 158 (98.8) | 85 (53.8) | 71 (44.9) | 1 (0.6) | 1 (0.6) |
G/A | 2 (1.2) | 1 (50.0) | 1 (50.0) | 0 | 0 |
NUDT15 p.Arg139Cys | |||||
C/C | 117 (73.1) | 68 (58.1) | 49 (41.9) | 0 | 0 |
C/T | 35 (21.9) | 15 (42.9) | 18 (51.4) | 1 (2.9) | 1 (2.9) |
T/T | 8 (5.0) | 3 (37.5) | 5 (62.5) | 0 | 0 |
NUDT15 p.Arg139His | |||||
G/G | 160 (100.0) | 86 (53.8) | 72 (45.0) | 1 (0.6) | 1 (0.6) |
G/A | 0 | 0 | 0 | 0 | 0 |
FTO p.Ala134Thr | |||||
G/G | 151 (94.3) | 82 (54.3) | 68 (45.0) | 1 (0.7) | 0 |
G/A | 9 (5.6) | 4 (44.4) | 4 (44.4) | 0 | 1 (11.1) |
RUNX1intergenic (rs2834826) | |||||
C/C | 60 (37.5) | 31 (51.7) | 29 (48.3) | 0 | 0 |
C/T | 80 (50.0) | 45 (56.3) | 33 (41.3) | 1 (1.3) | 1 (1.3) |
T/T | 20 (12.5) | 10 (50.0) | 10 (50.0) | 0 | 0 |
Values are presented as number (%).
IBDu, IBD unclassified.
Gene | NUDT15 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Coding SNP (location) | p.Val18_Val19insGlyVal (exon 1) | p.Val18Ile (exon 1) | p.Arg139Cys (exon 3) | |||||||
Type of variants | 6-bp insertion | P-value | Missense | P-value | Missense | P-value | ||||
Genotype | -/- | -/GGAGTC | G/G | G/A | C/C | C/T | T/T | |||
No. of patients | 116 (94.3) | 7 (5.7) | 121 (98.4) | 2 (1.6) | 93 (75.6) | 22 (17.9) | 8 (6.5) | |||
Male/female | 66/50 | 6/1 | 71/50 | 1/1 | 54/39 | 13/9 | 5/3 | |||
No GI intolerance | 107 (94.7) | 6 (5.3) | 111 (98.2) | 2 (1.8) | 86 (76.1) | 20 (17.7) | 7 (6.2) | |||
GI intolerance | 9 (90.0) | 1 (10.0) | 0.4562 | 10 (100.0) | 0 | - | 7 (70.0) | 2 (20.0) | 1 (10.0) | 0.8706 |
Values are presented as number (%).
GI, gastrointestinal; SNP, single nucleotide polymorphism.
Gene | NUDT15 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Coding SNP (location) | p.Val18_Val19insGlyVal (exon 1) | p.Val18Ile (exon 1) | p.Arg139Cys (exon 3) | |||||||
Type of variants | 6-bp insertion | P-value | Missense | P-value | Missense | P-value | ||||
Genotype | -/- | -/GGAGTC | G/G | G/A | C/C | C/T | T/T | |||
No. of patients | 139 (93.3) | 10 (6.7) | 147 (98.7) | 2 (1.3) | 109 (73.2) | 33 (22.1) | 7 (4.7) | |||
Male/female | 82/57 | 8/2 | 89/58 | 1/1 | 65/44 | 21/12 | 4/3 | |||
No leukopenia | 87 (96.7) | 3 (3.3) | 90 (100.0) | 0 | 80 (88.8) | 9 (10.0) | 1 (1.1) | |||
Leukopenia | 52 (88.1) | 7 (11.9) | 0.0512 | 57 (96.6) | 2 (3.4) | 0.1552 | 29 (49.1) | 24 (40.7) | 6 (10.2) | <0.0001 |
Early leukopenia | 14 (87.5) | 2 (12.5) | 0.1629 | 16 (100.0) | 0 | - | 3 (18.7) | 8 (50.0) | 5 (31.3) | <0.0001 |
Late leukopenia | 38 (88.4) | 5 (11.6) | 0.1113 | 41 (95.3) | 2 (4.7) | 0.1029 | 26 (60.5) | 16 (37.2) | 1 (2.3) | 0.0006 |
No severe hair loss | 132 (93.0) | 10 (7.0) | 140 (98.6) | 2 (1.4) | 109 (76.8) | 33 (23.2) | 0 | |||
Severe hair loss | 7 (100.0) | 0 | - | 7 (100.0) | 0 | - | 0 | 0 | 7 (100.0) | <0.0001 |
Values are presented as number (%).
SNP, single nucleotide polymorphism.
Gene | FTO | RUNX1 | |||||
---|---|---|---|---|---|---|---|
SNP (location) | p.Ala134Thr (exon 3) | RUNX1 intergenic (rs2834826) | |||||
Type of variants | Missense | P-value | Non coding variant | P-value | |||
Genotype | G/G | A/G | C/C | C/T | T/T | ||
No. of patients | 140 (94.0) | 9 (6.0) | 56 (37.6) | 73 (49.0) | 20 (13.4) | ||
Male/female | 84/56 | 6/3 | 35/21 | 46/27 | 9/11 | ||
No leukopenia | 85 (94.4) | 5 (5.6) | 33 (36.7) | 47 (52.2) | 10 (11.1) | ||
Leukopenia | 55 (93.2) | 4 (6.8) | 0.7404 | 23 (39.0) | 26 (44.1) | 10 (16.9) | 0.4869 |
Early leukopenia | 15 (93.7) | 1 (6.3) | - | 5 (31.2) | 8 (50.0) | 3 (18.8) | 0.6803 |
Late leukopenia | 40 (93.0) | 3 (7.0) | 0.7130 | 18 (41.9) | 18 (41.9) | 7 (16.3) | 0.4839 |
No severe hair loss | 133 (93.7) | 9 (6.3) | 52 (36.6) | 71 (50.0) | 19 (13.4) | ||
Severe hair loss | 7 (100.0) | 0 | 4 (57.1) | 2 (28.6) | 1 (14.3) | 0.5023 |
Values are presented as number (%).
SNP, single nucleotide polymorphism.
Values are presented as number (%), mean (range), or mean±SD. aNo leukopenia vs. leukopenia. IBDu, IBD unclassified; 5-ASA, 5-aminosalicylic acid; TNF-α, tumor necrosis factor α; AZA, azathioprine; 6-MP, 6-mercaptopurine.
Values are presented as number (%). IBDu, IBD unclassified.
Values are presented as number (%). GI, gastrointestinal; SNP, single nucleotide polymorphism.
Values are presented as number (%). SNP, single nucleotide polymorphism.
Values are presented as number (%). SNP, single nucleotide polymorphism.