PMID- 20015871
OWN - NLM
STAT- MEDLINE
DCOM- 20111005
LR  - 20211203
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 95
IP  - 5
DP  - 2010 May
TI  - Pharmacogenetic risk factors for altered bone mineral density and body 
      composition in pediatric acute lymphoblastic leukemia.
PG  - 752-9
LID - 10.3324/haematol.2009.016303 [doi]
AB  - BACKGROUND: This study investigates pharmacogenetic risk factors for bone mineral 
      (apparent) density (BM(A)D) and body composition in pediatric acute lymphoblastic 
      leukemia DESIGN AND METHODS: We determined the influence of SNPs in 4 genes 
      (vitamin-D receptor (VDR: BsmI/ApaI/TaqI and Cdx-2/GATA), collagen type I alpha 1 
      (SpI), estrogen receptor 1 (ESR1: PvuII/XbaI), glucocorticoid receptor (BclI)) on 
      body composition, BM(A)D and fracture risk during dexamethasone-based pediatric 
      acute lymphoblastic leukemia treatment. Body composition and BMD were measured 
      repeatedly during and after treatment using dual energy X-ray absorptiometry. 
      RESULTS: Non-carriers of VDR 5'-end (Cdx-2/GATA) haplotype 3 revealed a 
      significant larger fat gain than carriers (Delta%fat: non-carriers: +1.76SDS, 
      carriers: +0.77SDS, P<0.001). At diagnosis and during therapy, lumbar spine BMD 
      was significantly higher in non-carriers of VDR 5'-end (Cdx-2/GATA) haplotype 3 
      than in carriers. The other SNPs did not influence BMD or fracture risk 
      during/after treatment. The year after treatment completion, lean body mass 
      increased in non-carriers of ESR1 (PvuII/XbaI) haplotype 3 and decreased in 
      carriers (Delta lean body mass: non-carriers:+0.28SDS, carriers: -0.55SDS, 
      P<0.01). CONCLUSIONS: Only VDR 5'-end (Cdx-2/GATA) haplotype 3 was identified as 
      protective factor against excessive fat gain and as a risk factor for lower 
      lumbar spine BMD during treatment. Carrying ESR1 (PvuII/XbaI) haplotype 3 
      negatively influenced recovery of lean body mass after pediatric acute 
      lymphoblastic leukemia treatment.
FAU - te Winkel, Mariel L
AU  - te Winkel ML
AD  - Department of Pediatric Oncology/Hematology, Erasmus MC, Sophia Children's 
      Hospital, 3015 GJ Rotterdam, the Netherlands.
FAU - van Beek, Robert D
AU  - van Beek RD
FAU - de Muinck Keizer-Schrama, Sabine M P F
AU  - de Muinck Keizer-Schrama SM
FAU - Uitterlinden, Andre G
AU  - Uitterlinden AG
FAU - Hop, Wim C J
AU  - Hop WC
FAU - Pieters, Rob
AU  - Pieters R
FAU - van den Heuvel-Eibrink, Marry M
AU  - van den Heuvel-Eibrink MM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091216
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (COL1A1 protein, human)
RN  - 0 (Collagen Type I, alpha 1 Chain)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Receptors, Calcitriol)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Adolescent
MH  - Body Composition/drug effects/*genetics
MH  - Bone Density/drug effects/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Collagen Type I, alpha 1 Chain
MH  - Dexamethasone/adverse effects
MH  - Estrogen Receptor alpha/genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Genetic Variation/genetics
MH  - Humans
MH  - Infant
MH  - Male
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/*genetics
MH  - Prospective Studies
MH  - Receptors, Calcitriol/genetics
MH  - Risk Factors
PMC - PMC2864381
EDAT- 2009/12/18 06:00
MHDA- 2011/10/06 06:00
PMCR- 2010/05/01
CRDT- 2009/12/18 06:00
PHST- 2009/12/18 06:00 [entrez]
PHST- 2009/12/18 06:00 [pubmed]
PHST- 2011/10/06 06:00 [medline]
PHST- 2010/05/01 00:00 [pmc-release]
AID - haematol.2009.016303 [pii]
AID - 0950752 [pii]
AID - 10.3324/haematol.2009.016303 [doi]
PST - ppublish
SO  - Haematologica. 2010 May;95(5):752-9. doi: 10.3324/haematol.2009.016303. Epub 2009 
      Dec 16.