甲氨蝶呤,临床注释-2,变异和临床注释数据

甲氨蝶呤

临床注释ID

827848365

药物名称(英)

methotrexate

变异单倍型

rs1801133

基因

MTHFR

证据级别

水平覆盖

水平修饰符

Tier 1 VIP

表现型类别(英)

Toxicity

表现型类别

毒性

分数

23.25

PMID计数

计数的证据

表现型

药物毒性；血液毒性；白细胞减少症；淋巴瘤；粘膜炎；肿瘤；中性粒细胞减少症；骨肉瘤；前体细胞淋巴细胞白血病-淋巴瘤；原发性中枢神经系统淋巴瘤；血小板减少症；中毒性肝病

表现型(英)

Drug Toxicity;hematotoxicity;Leukopenia;Lymphoma;mucositis;Neoplasms;Neutropenia;Osteosarcoma;Precursor Cell Lymphoblastic Leukemia-Lymphoma;primary central nervous system lymphoma;Thrombocytopenia;Toxic liver disease

最新日期

2022/2/25 0:00:00

URL

https://www.pharmgkb.org/clinicalAnnotation/827848365

专业人口(英)

Pediatric

专业人口

儿科

临床等位基因

id	等位基因	注释文本
708	GG	Patients with the rs1801133 GG genotype and cancer who are treated with methotrexate may be at decreased risk of toxicity as compared to patients with the AA or AG genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of toxicity following methotrexate treatment. This drug-variant pair has been assigned a 鈥渘o recommendation鈥?by DPWG, as it was determined to be not clinically actionable.
707	AG	Patients with the rs1801133 AG genotype and cancer who are treated with methotrexate may be at increased risk of toxicity as compared to patients with the GG genotype, and may be at decreased risk of toxicity compared to patients with the AA genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of toxicity following methotrexate treatment. This drug-variant pair has been assigned a 鈥渘o recommendation鈥?by DPWG, as it was determined to be not clinically actionable.
706	AA	Patients with the rs1801133 AA genotype and cancer who are treated with methotrexate may be at increased risk of toxicity as compared to patients with the AG or GG genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of toxicity following methotrexate treatment. This drug-variant pair has been assigned a 鈥渘o recommendation鈥?by DPWG, as it was determined to be not clinically actionable.

临床证据

id	证据的ID	总结
305	1448997017	Genotype GG is associated with decreased risk of Drug Toxicity when treated with methotrexate in children with Neoplasms as compared to genotypes AA + AG.
304	1448124321	Genotype AA is not associated with risk of Neurotoxicity Syndromes when treated with methotrexate in children with Hematologic Neoplasms as compared to genotypes AG + GG.
303	1184514065	Allele G is not associated with risk of nephrotoxicity when treated with methotrexate in children with Leukemia as compared to allele A.
302	1184510310	Genotypes AA + AG is not associated with risk of non-hematological toxicity when treated with methotrexate in children with Lymphoma, Non-Hodgkin as compared to genotype GG.
301	1184169137	Allele A is not associated with risk of Toxic liver disease when treated with methotrexate in people with Neoplasms as compared to allele G.
300	1184169119	Genotypes AA + AG is associated with increased risk of Toxic liver disease when treated with methotrexate in children with Neoplasms as compared to genotype GG.
299	637879773	Genotype AA is associated with increased risk of mucositis when treated with methotrexate in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotypes AG + GG.
298	637879722	Genotype AA is associated with increased risk of mucositis when treated with methotrexate in people with Lymphoma, Non-Hodgkin as compared to genotypes AG + GG.
297	637879769	Genotype AA is associated with increased risk of Drug Toxicity when treated with methotrexate in people with Leukemia as compared to genotypes AG + GG.
296	981475997	Genotype AA is not associated with risk of Drug Toxicity when treated with methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AG + GG.
295	1451548770	Genotypes AG + GG are associated with increased severity of Leukopenia due to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype AA.
294	1451548500	Genotype AG is associated with increased risk of Drug Toxicity due to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
293	1451547222	Genotype AG is associated with increased risk of hematotoxicity due to methotrexate in people with primary central nervous system lymphoma as compared to genotype GG.
292	1451547041	Allele A is not associated with risk of mucositis, nephrotoxicity or Toxic liver disease due to methotrexate in children with Osteosarcoma as compared to allele C.
291	1447675071	Genotype GG is associated with increased risk of Toxic liver disease when treated with methotrexate in people with Osteosarcoma as compared to genotypes AA + AG.
290	1446898640	Genotypes AA + AG is associated with increased Drug Toxicity when treated with methotrexate in children with as compared to genotype GG.
289	1451635256	Allele A is not associated with risk of Drug Toxicity due to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C.
288	1451634220	Allele A is associated with increased risk of mucositis when treated with methotrexate in children with Lymphoma, Osteosarcoma or Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G.
287	1451553448	Genotype AA is associated with increased risk of hematotoxicity due to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
286	1451552860	Allele A is not associated with risk of Drug Toxicity due to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G.
285	1451511426	Genotypes AA + AG are associated with increased risk of Leukopenia or Thrombocytopenia due to methotrexate in children with Lymphoma, Non-Hodgkin as compared to genotype GG.
284	1451504586	Allele A is not associated with risk of Drug Toxicity due to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G.
283	655387891	Genotype AA is associated with increased risk of gastrointestinal toxicity, Leukopenia and Toxic liver disease when treated with methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
282	637879745	Genotype AA is associated with increased risk of Drug Toxicity when treated with methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AG + GG.
281	769146371	Genotype AA is associated with increased severity of mucositis when treated with methotrexate in people with hematopoietic stem cell transplantation as compared to genotype GG.
280	827829042	Genotype AA is associated with increased risk of toxicity when treated with methotrexate as compared to genotype GG.
279	637879736	Genotype AA is associated with increased risk of Thrombocytopenia or Toxic liver disease when treated with methotrexate in people with Lymphoma, Non-Hodgkin as compared to genotypes AG + GG.
278	1447979303	Genotypes AA + AG are associated with increased risk of Leukopenia or Neutropenia when treated with methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
277	1451465191	Genotypes AA + AG are associated with increased risk of Thrombocytopenia due to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
276	1451464465	Genotype AA is associated with increased risk of Neurotoxicity Syndromes and Toxic liver disease when treated with methotrexate in children with Osteosarcoma.
275	1184510298	Genotypes AA + AG is associated with increased risk of hematological toxicity when treated with methotrexate in children with Lymphoma, Non-Hodgkin as compared to genotype GG.
274	769171025	Genotypes AA + AG are associated with decreased severity of Leukopenia when treated with methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
273	751696635	Allele A is not associated with risk of Drug Toxicity when treated with methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G.
272	769170671	Genotypes AA + AG are associated with increased likelihood of treatment interruptions when treated with methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
271	1184746658	Genotypes AA + AG is associated with increased risk of Drug Toxicity when treated with methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.

临床病史

id	类型	评论
980	Update	added DPWG text.
979	Update	Added PMID 33841551 to evidence.
978	Update	Added PMID 34346513 to evidence.
977	Update	Added PMID 32695297 to evidence
976	Update	Added PMID 32612964 to evidence
975	Update	Added PMID 30684021 to evidence.
974	Update	Added PMID 29911750 to evidence
973	Update	Added PMID 27781293 to evidence. Updated phenotype tags
972	Update	Added PMID 27104192 to evidence
971	Update	Added PMID 25177243 to evidence.
970	Update	Added PMID 22074251 to evidence.
969	Update	Consolidated multiple VAs from same publication
968	Note	cross checked
967	Update	Added VAs from studies in adult cancer patients, marked conflicting evidence.
966	Update	Added PMID 21534867 to evidence. Awaiting curator check before approval.
965	Update	Added PMID 19031955 to evidence
964	Update	CA score added as part of scoring system release. LOE may have automatically changed based on new score but may be subject to further changes upon curator review.
963	Update	Added PMID 29683944

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