BACKGROUND: This study aims to identify folate-metabolism-related genetic risk factors for low bone mineral density (BMD) during/after pediatric acute lymphoblastic leukemia (ALL) treatment. PATIENTS AND METHODS: We investigated the influence of methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C) and methionine synthase reductase (MTRR 66A > G) single nucleotide polymorphisms (SNPs) on total body BMD (BMD(TB)) and lumbar spine BMD (BMD(LS)) in 83 patients. Homocysteine, folate and vitamin B12 were determined. BMD was measured repeatedly using dual-energy X-ray absorptiometry in patients ≥ 4 years (n = 68). RESULTS: Carriers of the MTHFR 677 T-allele showed a lower baseline BMD(TB) than non-carriers (-0.38 SDS vs. +0.55 SDS, p = 0.01) and BMD(TB) remained lower during/after treatment. MTHFR 677C>T did not influence treatment-related loss of BMD(TB) (p = 0.39). The MTRR 66 G-allele carriers showed a trend towards a lower BMD(TB) compared with non-carriers. Combining these two SNPs, patients carrying ≥ 2 risk alleles had a significantly lower BMD(TB) (-1.40 SDS) than patients with one (-0.80 SDS) or no risk alleles (-0.31 SDS). Although carriers of the MTHFR 1298A > C had higher homocysteine levels, this SNP was not related to BMD(TB). BMD(LS) of carriers was similar to non-carriers of the investigated SNPs. CONCLUSIONS: The MTHFR 677C>T SNP and the MTRR 66A >G SNP were identified as determinants of impaired BMD(TB) in childhood ALL patients. Crown
BACKGROUND: This study aims to identify folate-metabolism-related genetic risk factors for low bone mineral density (BMD) during/after pediatric acute lymphoblastic leukemia (ALL) treatment. PATIENTS AND METHODS: We investigated the influence of methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C) and methionine synthase reductase (MTRR 66A > G) single nucleotide polymorphisms (SNPs) on total body BMD (BMD(TB)) and lumbar spine BMD (BMD(LS)) in 83 patients. Homocysteine, folate and vitamin B12 were determined. BMD was measured repeatedly using dual-energy X-ray absorptiometry in patients ≥ 4 years (n = 68). RESULTS: Carriers of the MTHFR 677 T-allele showed a lower baseline BMD(TB) than non-carriers (-0.38 SDS vs. +0.55 SDS, p = 0.01) and BMD(TB) remained lower during/after treatment. MTHFR 677C>T did not influence treatment-related loss of BMD(TB) (p = 0.39). The MTRR 66 G-allele carriers showed a trend towards a lower BMD(TB) compared with non-carriers. Combining these two SNPs, patients carrying ≥ 2 risk alleles had a significantly lower BMD(TB) (-1.40 SDS) than patients with one (-0.80 SDS) or no risk alleles (-0.31 SDS). Although carriers of the MTHFR 1298A > C had higher homocysteine levels, this SNP was not related to BMD(TB). BMD(LS) of carriers was similar to non-carriers of the investigated SNPs. CONCLUSIONS: The MTHFR 677C>T SNP and the MTRR 66A >G SNP were identified as determinants of impaired BMD(TB) in childhood ALL patients. Crown
Authors: Hiroto Inaba; Xueyuan Cao; Alice Q Han; John C Panetta; Kirsten K Ness; Monika L Metzger; Jeffrey E Rubnitz; Raul C Ribeiro; John T Sandlund; Sima Jeha; Cheng Cheng; Ching-Hon Pui; Mary V Relling; Sue C Kaste Journal: Cancer Date: 2017-12-19 Impact factor: 6.860
Authors: Marissa A H den Hoed; Saskia M F Pluijm; Mariël L te Winkel; Hester A de Groot-Kruseman; Martha Fiocco; Peter Hoogerbrugge; Jan A Leeuw; Marrie C A Bruin; Inge M van der Sluis; Dorien Bresters; Maarten H Lequin; Jan C Roos; Anjo J P Veerman; Rob Pieters; Marry M van den Heuvel-Eibrink Journal: Haematologica Date: 2015-09-24 Impact factor: 9.941
Authors: Jenneke E van Atteveld; Demi Tc de Winter; Rob Pieters; Sebastian Jcmm Neggers; Marry M van den Heuvel-Eibrink Journal: Fac Rev Date: 2021-06-23
Authors: Poliana Cristina Carmona Molinari; Henrique Manoel Lederman; Maria Lucia de Martino Lee; Eliana Maria Monteiro Caran Journal: Rev Paul Pediatr Date: 2017-02-20