Faculty of Pharmacy, Shiraz University of Medical Sciences, Iran.
Clin Ther. 2011 Mar;33(3):280-90. doi: 10.1016/j.clinthera.2011.03.004. Epub 2011 Apr 17.
Glucocorticoids are an important component of treatment for childhood acute lymphoblastic leukemia (ALL). To induce antileukemic effects, glucocorticoids have to bind their intracellular receptors. Little is known about probable mechanisms of glucocorticoid resistance in ALL.
The aim of this study was to evaluate the possible association between 3 prominent glucocorticoid receptor gene polymorphisms-BclI, N363S, and ER22/23EK-and the risk of relapse in children with ALL.
We conducted a case-control study on 100 children with ALL, aged 0 to 15 years, including 50 nonrelapsed (control) and 50 relapsed (case) subjects. Required patient information such as demographic characteristics; relevant clinical and paraclinical findings at diagnosis; chemotherapy protocols used at diagnosis; and relapse properties, including time interval from date of initial diagnosis to relapse and number, type, and site of relapse, were gathered from patients' medical files. Genotyping of BclI, N363S, and ER22/23EK polymorphisms was carried out by polymerase chain reaction restriction fragment-length polymorphism (PCR-RFLP). Statistical analysis was performed. The distribution of BclI, N363S, and ER22/23EK polymorphism genotypes in our population and in populations examined in similar studies was compared using the χ(2) test or Fischer exact test.
One hundred children with ALL, consisting of 65 males and 35 females, were recruited into this study. Their mean (SD) age was 5.39 (3.02) years. No relapsed or nonrelapsed individuals were homozygous for N363S and ER22/23EK polymorphisms. The allelic frequencies of mutant alleles of BclI, N363S, and ER22/23EK polymorphisms in all patients were 0.195, 0.02, and 0.005, respectively. No statistically significant association between BclI, N363S, and ER22/23EK polymorphisms and risk of relapse in children with ALL was observed (P = 0.104 [BclI], not calculated for the last 2 polymorphisms [N363S and ER22/23EK]). The incidence of BclI polymorphism in our population (35/100) differed significantly from that in a Canadian population with European descent (135/219) and a Dutch population (29/53) (P < 0.001 and P = 0.007, respectively).
Our data suggest that there did not appear to be any prognostic value of BclI, ER22/23EK, and N363S polymorphisms for predicting relapse in this population of 100 Iranian children with ALL.
糖皮质激素是治疗儿童急性淋巴细胞白血病（ALL）的重要组成部分。为了产生抗白血病作用，糖皮质激素必须与其细胞内受体结合。关于 ALL 中糖皮质激素耐药的可能机制知之甚少。
本研究旨在评估 3 种主要糖皮质激素受体基因多态性（BclI、N363S 和 ER22/23EK）与 ALL 患儿复发风险之间的可能关联。
我们对 100 名 0 至 15 岁的 ALL 患儿进行了病例对照研究，包括 50 名未复发（对照组）和 50 名复发（病例组）患儿。从患者的病历中收集了人口统计学特征；诊断时的相关临床和实验室检查结果；诊断时使用的化疗方案；以及复发特征，包括从初始诊断到复发的时间间隔、复发的次数、类型和部位。BclI、N363S 和 ER22/23EK 多态性的基因分型通过聚合酶链反应限制性片段长度多态性（PCR-RFLP）进行。进行了统计学分析。通过 χ(2)检验或 Fisher 确切检验比较我们人群与类似研究中检查人群的 BclI、N363S 和 ER22/23EK 多态性基因型分布。
本研究纳入了 100 名 ALL 患儿，其中 65 名男性和 35 名女性。他们的平均（SD）年龄为 5.39（3.02）岁。没有复发或未复发的个体是 N363S 和 ER22/23EK 多态性的纯合子。所有患者的 BclI、N363S 和 ER22/23EK 多态性突变等位基因的等位基因频率分别为 0.195、0.02 和 0.005。未观察到 BclI、N363S 和 ER22/23EK 多态性与 ALL 患儿复发风险之间存在统计学显著关联（P = 0.104[BclI]，后两种多态性[未计算 N363S 和 ER22/23EK]）。我们人群中 BclI 多态性的发生率（35/100）与加拿大具有欧洲血统的人群（219/135）和荷兰人群（53/29）有显著差异（P < 0.001 和 P = 0.007）。
我们的数据表明，BclI、ER22/23EK 和 N363S 多态性似乎对伊朗 100 名 ALL 患儿的复发没有预测价值。
