Validations of Top and Novel Susceptibility Variants in All-Age Chinese Patients With Acute Lymphoblastic Leukemia
Validations of Top and Novel Susceptibility Variants in All-Age Chinese Patients With Acute Lymphoblastic Leukemia
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中国全年龄段急性淋巴细胞白血病患者的主要和新的易感性变异的验证
DOI：
10.3389/fgene.2020.01004
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发表时间：
2020-08-25
影响因子：
3.7
通讯作者：
Lu, Xiaoxi
中科院分区：
文献类型：
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作者：
Liao, Fei;Ye, Yuanxin;Lu, Xiaoxi
通过全基因组关联研究（GWAS），已在儿童中确定了多种急性淋巴细胞白血病（ALL）的遗传易感性。最近，在ERG上定位到一个新的易感位点，呈现出西班牙裔特异性。在本研究中，我们对所有年龄段的中国患者（N = 451）进行了一项重复研究，不仅验证了新的ERG位点，还系统地确定了年龄对主要GWAS信号关联状态的影响。我们发现ARID5B、IKZF1、CEBPE、PIP4K2A的单核苷酸多态性仅与无BCR - ABL融合的儿童患者的ALL易感性显著相关，而GATA3信号在成人中无论是否携带BCR - ABL融合都具有显著意义。此外，新的ERG单核苷酸多态性在无BCR - ABL和ETV6 - RUNX1融合的儿童患者中得到验证。我们的研究结果表明年龄对ALL遗传易感性具有修饰作用，并强调了ERG单核苷酸多态性对中国患者的影响。
Through genome-wide association studies (GWAS), multiple inherited predispositions to acute lymphoblastic leukemia (ALL) have been identified in children. Most recently, a novel susceptibility locus atERGwas localized, exhibiting Hispanic-specific manner. In this study, we conducted a replication study to in all-age Chinese patients (N= 451), not only validating the novelERGlocus, but also systematically determining the impact of age on association status of the top GWAS signals. We found that single nucleotide polymorphisms atARID5B,IKZF1,CEBPE,PIP4K2Awere only significantly associated with ALL susceptibility in childhood patients with noBCR-ABLfusion, whileGATA3signal exhibited its significance in adults no matter carryingBCR-ABLfusion or not. Moreover, the novelERGSNP can be validated in pediatric patients without bothBCR-ABLandETV6-RUNX1fusion. Our finding suggests the modifying effects of age on genetic predisposition to ALL, and highlights the impact ofERGSNP in Chinese patients.