Centre de recherche Charles Bruneau, Montréal, Québec, Canada.
Leuk Res. 2010 Apr;34(4):492-7. doi: 10.1016/j.leukres.2009.08.007. Epub 2009 Sep 16.
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.
对 310 例儿童急性淋巴细胞白血病患者进行了 NR3C1 基因中的四个 SNP 分析。-627A/G、内含子 2+646C/G 和 9bT/C 多态性均与无事件生存降低相关。由这些位点的 AGT 等位基因组成的单体型，并由内含子 2+646G 变异体标记，也与较低的无事件生存相关（p=0.03）。这种单体型对结局的渐进影响与与两个拷贝相关，与总生存降低相关（p=0.05）。在淋巴母细胞系中的定量 mRNA 分析表明，AGT 单体型的携带者具有更高比例的 GR gamma/alpha 同工型（p=0.04），这可能解释了其与无事件生存和总生存降低的关联。
