Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation.
To evaluate whether the C677T and A1298C polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of methotrexate (MTX) used in allogeneic stem cell transplantation, we performed association analysis between these genetic polymorphisms and the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation. Patients (n=72) with hematological malignancy or aplastic anemia were given a short course of MTX as a graft-versus-host disease prophylaxis. Patients with the 677TT genotype showed higher total bilirubin levels (677TT vs 677CT vs 677CC, 14.5 vs 8.6 vs 3.8 mg/dl, respectively; p=0.07) and higher aspartic transaminase levels (677TT vs 677CT vs 677CC, 678.9 vs 156.6 vs 111.8 IU/l; p=0.04). Platelet recovery to 20,000/mul was slower for patients with the 677TT genotype than for patients with other genotypes (677TT, 59 days; 677CT, 26 days; 677CC, 26 days; p=0.0075). The influences of the C677T polymorphism on treatment-related mortality (TRM) were also analyzed. One-year cumulative TRMs for patients with the TT genotype and the other genotypes were 66 and 30% (p=0.04) and their respective 1-year overall survivals were 30 and 56% (p=0.11). No association was observed between the A1298C polymorphism and clinical outcome for any of the different genotypes. Therefore, patients at high risk of developing hepatic toxicity and with a poor likelihood of survival could be selected by genotyping MTHFR C677T before allogeneic stem cell transplantation.
Kim
Inho
I
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, South Korea.
Lee
Kyung-Hun
KH
Kim
Jin Hee
JH
Ra
Eun Kyung
EK
Yoon
Sung-Soo
SS
Hong
Yun-Chul
YC
Park
Sung Sup
SS
Kim
Chul Soo
CS
Park
Seonyang
S
Kim
Byoung Kook
BK
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000401:mortality; D016896:Treatment Outcome
D042965:Methylenetetrahydrofolate Reductase (NADPH2)