title: 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
  
  
  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.
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC, Sophia Children's Hospital, 3015 GJ Rotterdam, the Netherlands.
authors.forename: Mariël L
authors.initials: ML
authors.lastname: te Winkel
authors.forename: Robert D
authors.initials: RD
authors.lastname: van Beek
authors.forename: Sabine M P F
authors.initials: SM
authors.lastname: de Muinck Keizer-Schrama
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D000293:Adolescent; D001823:Body Composition / Q000187:drug effects / Q000235:genetics*; D015519:Bone Density / Q000187:drug effects / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000090602:Collagen Type I, alpha 1 Chain; D003907:Dexamethasone / Q000009:adverse effects; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics; D012307:Risk Factors
chemical_list: C000716127:COL1A1 protein, human; D000090602:Collagen Type I, alpha 1 Chain; D047628:Estrogen Receptor alpha; D018167:Receptors, Calcitriol; D003907:Dexamethasone