BRD7基因在急性白血病细胞中的表达及SNP分析

Expression and SNP analysis of BRD7 gene in acute leukemia cells

目的：探讨BRD7基因在急性白血病（AL）患者骨髓单个核细胞（BMNCs）中的表达水平及单核苷酸多态性（SNP）分布。方法：采用半定量RT-PCR方法检测52例AL患者及30例非恶性血液病对照的BMNCs BRD7基因的表达水平，并应用单链构象多态性加直接测序法检测BRD7基因点突变或SNP，分析BRD7基因与AL的相关性。结果：在52例AL患者和30例对照组患者中均存在BRD7基因表达。急性淋巴细胞白血病（ALL）患者和急性非淋巴细胞白血病（ANLL）患者BRD7 mRNA的相对表达量均高于对照组（P=0．001；P=0.037）。BRD7基因编码区（447～844bp）存在3个cSNPs，即C657A，C495T和A737G，其中C495T和A737G偶联发生。C657A多态性的基因频率在AL组和对照中差异无统计学意义。两个偶联的SNPs等位基因频率及基因型频率在AL组和对照中差异存在统计学意义（P〈0．01）；但在AL组中3种基因型之间BRD7 mRNA的表达差异无统计学意义（P〉0．05）。结论：BRD7基因在急性白血病患者细胞中表达上调。BRD7基因编码区（447～844 bp）2个偶联SNPs（C495T和A737G）与AL存在相关性，可能是AL的遗传易感因子之一。

Objective To evaluate the expression level of BRD7 gene in bone marrow mononuclear cells （BMNCs） in patients with acute leukemia （AL） and to analyze BRD7 single nucleotide polymorphism（ SNP）. Methods RT-PCR was used to detect BRD7 expression in patients with AL and normal bone marrow subjects. Single-strand conformation polymorphism and DNA sequence analysis were also used to identify BRD7 mutation or SNP to investigate the relation between BRD7 and AL.Results BRD7 mRNA in BMNCs from 52 patients with AL and 30 control subjects was expressed. The mRNA relative expression of BRD7 in patients with AL was higher than that of the control group （P=0.001）. Three SNPs （C657A, C495T and A737G） in BRD7 gene coding region （447-844 bp）were found, and A737G was coupled with C495T. The allele frequencies of SNP C657A were not significantly different between AL and the control group. The genotype and the allele frequencies of the 2 coupled SNPs were significantly different （P〈0.01）. But there was no significant discrepancy among the mRNA expression levels of AA, AG, and GG genotypes in the leukemia group （P〉0.05）. Conclusion Expression of BRD7 gene is up-regulated in AL cells. The 2 coupled SNPs （ C495T and A737G ）in BRD7 gene coding region（447-844 bp） are correlated with AL, indicating that SNPs may be one of the genetic susceptibility factors of AL.