Correlations between the polym

Objective: To investigate the correlation between polymorphisms of serine hydroxymethyltransferasel gene and the adverse reactions of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods: A total of 51 patients with ALL were treated with HD-MTX, and clinical manifestations after HD-MTX treatment were evaluated retrospectively. cDNA was obtained from mRNA. The polymorphisms of SHMT1 gene containing rs1979277, rs3783, rs1979276, and rs12952556 sites were tested by denaturing gradient gel electrophoresis and direct sequencing. Effects of SHMT1 gene polymorphisms on HD-MTX adverse reactions were evaluated. Results: Severe adverse reactions in ALL patients treated with HD-MTX appeared to be mainly neutropenia and hepatoadverse reactions. The frequency distributions of rs3783 (OG), rs1979276 (C>T), rs12952556 (A>G), and rs1979277 C>T were the same. The polymorphisms of rs 1979277 showed no correlation with neutropenia (P>0.05) but rs 1979277 CT and TT genotypes were correlated with hepatoadverse reactions (CT: OR=0.129, 95% CI: 0.020 to 0.817, P=0.03; TT: OR=0.103, 95% Cl: 0.017 to 0.620, P=0.013). Conclusion: No correlation was found between the combination of rs1979277, rs3783, rsl979276, rs 12952556, and neutropenia, but one or more of these loci may reduce the risk of hepatoadverse reactions.