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Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia.


ABSTRACT: 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.

SUBMITTER: te Winkel ML 

PROVIDER: S-EPMC2864381 | BioStudies | 2010-01-01

REPOSITORIES: biostudies

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