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Original Article: Clinical

Single nucleotide polymorphisms in non-coding region of the glucocorticoid receptor gene and prednisone response in childhood acute lymphoblastic leukemia

, , , , , , , & show all
Pages 1704-1709 | Received 03 Mar 2014, Accepted 31 Jul 2014, Published online: 11 Feb 2015
 

Abstract

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.

Acknowledgements

We are thankful to all the patients and their parents who consented to participate in this study. This work was supported by the National Nature Scientific Foundation of China (81471888) and Pediatric Research Project of the First Hospital of Jilin University of China (2012069).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

Supplementary material available online

Supplementary Table 1 showing primer sequences and Supplementary Figure 1 showing linkage disequilibrium data

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