Wu Hongchun, Deng Jieqiong, Zheng Jian, You Yonghe, Li Na, Li Wei, Wu Depei, Zhou Yifeng
Laboratory of Cancer Molecular Genetics, Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
Mol Carcinog. 2015 Feb;54(2):102-10. doi: 10.1002/mc.22078. Epub 2013 Sep 4.
CD44 is such one adhesion molecule that mediates interactions between acute myeloid leukemia (AML) cells and stromal. It has been demonstrated that CD4 plays a critical role in AML development. However, studies of functional single nucleotide polymorphisms (SNPs) in CD44 gene have not touched upon AML. This case-control study probed the contribution of functional SNPs in CD44 gene to AML susceptibility in eastern Chinese population. Five representative SNPs of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were opted and genotyped in 421 AML patients and 461 healthy subjects and the association with risk of AML was estimated by logistic regression. Moreover, the potential role of rs13347C > T in AML was further explored. Compared with the rs13347CC genotype, CT carriers had a significant increase in AML susceptibility (adjusted odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.32-2.34), TT carriers had a further increased risk of AML (OR = 2.67; 95% CI = 1.69-4.21). Furthermore, our transient transfection assay and Western blot results demonstrated that the presence of rs13347T allele led to more CD44 expression. Yet, there exists no significant difference in genotype frequencies of the other four sites between cases and controls. Above findings suggest that rs13347C>T in 3'UTR of CD44 may be a genetic modifier for developing AML.
CD44是一种介导急性髓系白血病（AML）细胞与基质之间相互作用的黏附分子。已有研究表明，CD4在AML发展中起关键作用。然而，关于CD44基因功能性单核苷酸多态性（SNP）的研究尚未涉及AML。本病例对照研究探讨了CD44基因功能性SNP对中国东部人群AML易感性的影响。选择了CD44的五个代表性SNP（rs10836347C>T、rs13347C>T、rs1425802A>G、rs11821102G>A、rs713330T>C），对421例AML患者和461例健康受试者进行基因分型，并通过逻辑回归评估其与AML风险的关联。此外，进一步探讨了rs13347C>T在AML中的潜在作用。与rs13347CC基因型相比，CT携带者的AML易感性显著增加（校正比值比[OR]=1.76；95%置信区间[CI]=1.32-2.34），TT携带者的AML风险进一步增加（OR=2.67；95%CI=1.69-4.21）。此外，我们的瞬时转染试验和蛋白质印迹结果表明，rs13347T等位基因的存在导致更多的CD44表达。然而，病例组和对照组在其他四个位点的基因型频率没有显著差异。上述研究结果表明，CD44 3'UTR中的rs13347C>T可能是AML发生的遗传修饰因子。
