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Germline variation in the MTHFR and MTRR genes determines the nadir of bone density in pediatric acute lymphoblastic leukemia: a prospective study.
- Source :
-
Bone [Bone] 2011 Mar 01; Vol. 48 (3), pp. 571-7. Date of Electronic Publication: 2010 Oct 16. - Publication Year :
- 2011
-
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.<br />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).<br />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.<br />Conclusions: The MTHFR 677C>T SNP and the MTRR 66A >G SNP were identified as determinants of impaired BMD(TB) in childhood ALL patients.<br /> (Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2763
- Volume :
- 48
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Bone
- Publication Type :
- Academic Journal
- Accession number :
- 20955826
- Full Text :
- https://doi.org/10.1016/j.bone.2010.10.163