1. Germline variation in the MTHFR and MTRR genes determines the nadir of bone density in pediatric acute lymphoblastic leukemia: a prospective study.
- Author
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te Winkel ML, de Muinck Keizer-Schrama SM, de Jonge R, van Beek RD, van der Sluis IM, Hop WC, Pieters R, and van den Heuvel-Eibrink MM
- Subjects
- Absorptiometry, Photon, Adolescent, Biomarkers, Tumor genetics, Case-Control Studies, Child, Child, Preschool, Folic Acid metabolism, Fractures, Bone complications, Fractures, Bone genetics, Genotype, Homocysteine metabolism, Humans, Infant, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnostic imaging, Prospective Studies, Vitamin B 12 metabolism, Bone Density genetics, Ferredoxin-NADP Reductase genetics, Germ Cells metabolism, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Polymorphism, Single Nucleotide genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma enzymology, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
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 Copyright © 2010. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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