TABLE 1.
Reported characteristics of patients with homozygous variant NUDT15 c.415C>T genotypes taking azathioprine (AZA).
| No. | Source | Age/Gender | Disease | TPMT genotype | NUDT15 c.415C>T genotype | AZA dose | Interval a and neutrophil counts (× 109 cells/L) | The lowest NEU b counts (× 109 cells/L) | Recovery period (NEU count above 0.5×109 cells/L or 0.1×109 cells/L) after discontinuation c (other details) |
|---|---|---|---|---|---|---|---|---|---|
| Ethnicity | |||||||||
| Weight | |||||||||
| 1 | This report | 18 Female | SLE d | *2, c.238G>C(GG); *3B, c.460G>A(GG); *3C, c.719A>G(AA) | TT | 2.32 mg/kg/d | 27 d 0.43 | 0.00 | 12 d, 7 d (Neutrophil count 2.42 × 109 cells/L at day 18 after discontinuation) |
| Chinese | |||||||||
| 43 kg | |||||||||
| 2 | Séverine et al. (2022) | 26 Female | CD e | *2, c.238G>C(GG) | TT | 2.5 mg/kg/d | 35–42 d 0.66 | ∼0.3 | ? (Neutrophil count 1.5 × 109 cells/L at day 4 after discontinuation ( |
| European | *3B, c.460G>A(GG) | ||||||||
| ? | *3C, c.719A>G(AA) | ||||||||
| 3 | Bae et al. (2020) | 12 Female | CD | TPMT *1/*1 | TT | 0.5 mg/kg/d | ∼20 d 3.37 (due to significant hair loss) | ? | ? |
| Korean | |||||||||
| 34 kg | |||||||||
| 4 | Yan et al. (2018) | 47 Male | PV f | TPMT *1/*1 | CT | 150 mg/d | 65 d ? | ? | ? |
| Chinese | |||||||||
| ? | |||||||||
| 5 | Shih et al. (2019) | 28 Female | PV | TPMT *1/*1 | TT | 100 mg/d | 28 d 0.36 | 0.36 | ? |
| Chinese | |||||||||
| ? | |||||||||
| 40 Female | PV | TPMT *1/*1 | TT | 100 mg/d | 28 d 0.3 | 0.3 | ? | ||
| Chinese | |||||||||
| ? | |||||||||
| 6 | Nomura et al. (2018) | 61 Female | PV | ? | TT | 100 mg/d | 14 d ? | 0.435 | 8 d |
| Japanese | |||||||||
| ? | |||||||||
| 57 Female | PV | ? | TT | 100 mg/d | 17 d ? | 0.21 | 10 d | ||
| Japanese | |||||||||
| ? | |||||||||
| 37 Female | RA g | ? | TT | 50 mg/d twice a week | 46 d ? | 1.34 | 5 d | ||
| Japanese | |||||||||
| ? | |||||||||
| 7 | Hon et al. (2018) | 17 Female | Eczema | TPMT *1/*1 | TT | 50 mg/d | 28 d 0.8 | 0.1 | ? (Neutrophil count 1.8 × 109 cells/L at day 7 after discontinuation) |
| Chinese | |||||||||
| 70 kg | |||||||||
| 8 | Devasia et al. (2020) | 26 Female | AIHA h | *2, c.238G>C(GG) | TT | 1.5 mg/kg/d | 7 d 0.19 | ? | ? (Presented with hair loss, oral ulcers, and leukopenia) |
| Indian | *3B, c.460G>A(GG) | ||||||||
| ? | *3C, c.719A>G(AA) | ||||||||
| 28 Female | Chronic ITP i | *2, c.238G>C(GG) | TT | 1.5 mg/kg/d | 14 d 0.21 | ? | ? (Presented with hair loss and leukopenia) | ||
| Indian | *3B, c.460G>A(GG) | ||||||||
| ? | *3C, c.719A>G(AA) | ||||||||
| 34 Female | Chronic ITP | *2, c.238G>C(GG) | TT | 2 mg/kg/d | 14 d 0.19 | ? | ? (Presented with fever and cytopenia) | ||
| Indian | *3B, c.460G>A(GG) | ||||||||
| ? | *3C, c.719A>G(AA) | ||||||||
| 18 Female | Chronic ITP | *2, c.238G>C(GG) | CT | 1.5 mg/kg/d | 21 d 1.68 | ? | ? (Presented with hair loss, blood counts were normal, reduced doses of 1 mg/kg/d were tolerated) | ||
| Indian | *3B, c.460G>A(GG) | ||||||||
| ? | *3C, c.719A>G(AA) | ||||||||
| 12 Female | Chronic ITP | *2, c.238G>C(GG) | CT | 2 mg/kg/d | 28 d 0.8 | ? | ? (Presented with hair loss and leukopenia, lost to follow-up) | ||
| Indian | *3B, c.460G>A(GG) | ||||||||
| ? | *3C, c.719A>G(AA) | ||||||||
| 9 | Fei et al. (2018) | 22 Female | SS j | *3C, c.719A>G(AA) | TT | 0.91 mg/kg/d | 21 d 0.5 | 0.1 | 5 d, 3 d (Neutrophil count of 2.0 × 109/L at day 10 after discontinuation) |
| Chinese | |||||||||
| 55 kg | |||||||||
| 10 | Ben Salem et al. (2020) | 42 Male | IBD k | ? | TT | 2.27 mg/kg/d | 21 d 0.64 (White blood cell count) | ? | (White blood cell count of 5.5 × 109/L at day 10 after discontinuation) |
| Tunisian | |||||||||
| ? |
Interval: from taking AZA to discovery of myelosuppression.
NEU: Neutrophils.
NEU count above 0.5×109/L or 0.1×109/L.
SLE: Systematic lupus erythematosus.
CD: Crohn’s disease.
PV: Pemphigus vulgaris.
RA: Rheumatoid arthritis.
AIHA: autoimmune hemolytic anemia.
ITP: Idiopathic thrombocytopenic purpura.
SS: Sjögren syndrome.
IBD: inflammatory bowel disease; ?: not mentioned. Case reports of patients who took other medicine interacting with AZA, such as allopurinol (Takeuchi et al., 2021) or patients with abnormal liver function (Ailing et al., 2016) are not listed in this table. Other vaiants of NUDT15, such as NUDT15 416G>A (Tomiyoshi et al., 2020), are also not listed.