Polymorphisms in glucocorticoid receptor gene and the outcome of childhood acute lymphoblastic leukemia (ALL).
Childhood acute lymphoblastic leukemia patients (n=310) were analyzed for four SNPs in the NR3C1 gene. Polymorphisms -627A/G, intron 2 +646C/G and 9bT/C were all associated with reduced event-free survival. Haplotypes composed of AGT alleles at these loci and tagged by the intron 2 +646G variant also associated with lower event-free survival (p=0.03). The progressive impact of this haplotype on outcome was seen with two copies associated with reduced overall survival (p=0.05). Quantitative mRNA analysis in lymphoblastoid cell lines showed that carriers of the AGT haplotype had a higher ratio of GR gamma/alpha isoforms (p=0.04), which possibly explains its association with reduced event-free survival and overall survival.
Labuda
Malgorzata
M
Centre de recherche Charles Bruneau, Montréal, Québec, Canada.
Gahier
Annabel
A
Gagné
Vincent
V
Moghrabi
Albert
A
Sinnett
Daniel
D
Krajinovic
Maja
M
D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008297:Male; D017063:Outcome Assessment, Health Care; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D016019:Survival Analysis
C497713:NR3C1 protein, human; D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid