Xue Lu, Li Chunhuai, Wang Yue, Sun Wei, Ma Cui, He Yongyan, Yu Yongli, Cai Lu, Wang Liying
Department of Childhood Hematology and Oncology.
Leuk Lymphoma. 2015 Jun;56(6):1704-9. doi: 10.3109/10428194.2014.951848. Epub 2015 Feb 11.
Poor prednisone response predicts an inferior outcome in pediatric acute lymphoblastic leukemia (ALL) in Berlin-Frankfurt-Münster (BFM) treatment protocols. Here, we investigated five single nucleotide polymorphisms (SNPs) in both the coding and non-coding regions of the glucocorticoid receptor (GR) gene, and analyzed their association with prednisone responsiveness in vivo in 63 pediatric patients with ALL in China. Of the five SNPs, the rs41423247 and rs7701443 polymorphisms were significantly associated with prednisone response at the allelic level (rs41423247 odds ratio [OR] = 9.58; 95% confidence interval [CI]: 1.23-74.21; p = 0.01; rs7701443 OR = 3.12; 95% CI: 1.08-9; p = 0.02). Two polymorphisms (rs6189/6190 and rs6198) were not observed in the study cohort. Haplotypes composed of CCC alleles and TCG alleles at three loci (rs7701443, Tth111I and BclI) were both associated with prednisone response (p = 0.013; p = 0.028). Our results suggested that polymorphisms in the non-coding region of the GR gene were associated with prednisone response in vivo in pediatric ALL in Han Chinese.
在柏林-法兰克福-明斯特（BFM）治疗方案中，泼尼松反应不佳预示着儿童急性淋巴细胞白血病（ALL）的预后较差。在此，我们研究了糖皮质激素受体（GR）基因编码区和非编码区的五个单核苷酸多态性（SNP），并分析了它们与中国63例ALL患儿体内泼尼松反应性的相关性。在这五个SNP中，rs41423247和rs7701443多态性在等位基因水平上与泼尼松反应显著相关（rs41423247优势比[OR]=9.58；95%置信区间[CI]：1.23 - 74.21；p = 0.01；rs7701443 OR = 3.12；95% CI：1.08 - 9；p = 0.02）。研究队列中未观察到两个多态性（rs6189/6190和rs6198）。由三个位点（rs7701443、Tth111I和BclI）的CCC等位基因和TCG等位基因组成的单倍型均与泼尼松反应相关（p = 0.013；p = 0.028）。我们的结果表明，GR基因非编码区的多态性与中国汉族儿童ALL体内泼尼松反应相关。
