WNK1基因rs11611246位点多态性与云南汉族儿童急性淋巴细胞白血病关联性研究  

Association between polymorphism at rs11611246 site of WNK1 gene and acute lymphocytic leukemia in children of Han nationality in Yunnan province

作　　者：武坤[1] 苏艳丹 杨金荣[4,5] 王雪娇 曾云[4,5] WU Kun;SU Yan-Dan;YANG Jin-Rong;WANG Xue-Jiao;ZENG Yun(Department of Chinical Laboratory,First Affiliated Hospital of Kunming Medical University,Kunming 650032,China)

机构地区：[1]昆明医科大学第一附属医院医学检验科,昆明650032 [2]云南省检验医学重点实验室,昆明650032 [3]云南省实验诊断研究所,昆明650032 [4]昆明医科大学第一附属医院血液科,昆明650032 [5]云南省血液病研究中心,昆明650032

出　　处：《中国免疫学杂志》2020年第13期1619-1624,共6页Chinese Journal of Immunology

基　　金：云南省联合专项基金[No.2017FE468(-035)];云南省卫生科技计划资助项目(2016NS047,2018NS0129)资助。

摘　　要：目的:分析云南汉族人群急性淋巴细胞白血病(ALL)患儿WNK1基因rs11611246位点多态性,并探讨此基因位点多态性与ALL发病关系。方法:选择昆明医科大学第一附属医院2012年1月~2014年1月收治的首诊ALL患儿86例为研究对象,另选择同期健康患儿95例为健康对照组,收集相关资料,采用TaqMan-MGB探针等位基因分型技术分析rs11611246位点多态性,免疫印迹法检测ALL患者骨髓WNK1蛋白表达,并进行统计学分析。结果:ALL患儿与健康儿童rs11611246位点GG型、GT型、TT型等位基因均符合Hardy-Weinberg遗传平衡规律,GG型基因会显著增加儿童ALL患病风险(OR:2.002,95%CI:1.517~2.853,P=0.012),合并分析后发现G等位基因ALL发病风险是T等位基因2.189倍(95%CI:1.583~2.971,P=0.008)。GG型基因与“出生后居室装修”、“放射性物质接触”有协同交互作用(P<0.05)。GG型、GT/TT型患儿第1疗程诱导治疗完全缓解率无显著差异,但是GG型患儿5年无复发生存率、5年无事件生存率及5年总生存率显著低于GT/TT型患儿(P<0.05)。GG型患儿骨髓细胞WNK1蛋白表达显著低于GT型、TT型(P<0.05)。结论:WNK1基因rs11611246位点多态性与儿童ALL易感性相关,与部分环境因素呈协同交互作用,对患儿预后有一定影响。Objective:To analyze the polymorphism of WNK1 gene rs11611246 locus in children with acute lymphocytic leukemia(ALL)of Han nationality in Yunnan and to explore the relationship between the polymorphism of this gene locus and the pathogenesis of ALL.Methods:86 children with ALL admitted to the First Affiliated Hospital of Kunming Medical University from January 2012 to January 2014 were selected as research objects,and 95 healthy children in the same period were selected as the healthy control group.Relevant data were collected.Polymorphism at rs11611246 site was analyzed by TaqMan-MGB probe allelic typing technique,and WNK1 protein expression in bone marrow of ALL patients was detected by Western blot,and statistical analysis was carried out.Results:GG type,GT type and TT type alleles at rs11611246 locus in children with ALL and healthy children all conform to Hardy-Weinberg genetic balance rules.GG type genes could significantly increase the risk of childhood ALL,(OR:2.002,95%CI:1.517-2.853,P=0.012).Combined analysis showed that risk of G allele ALL was 2.189 times that of T allele,(95%CI:1.583-2.971,P=0.008).GG gene had synergistic interaction with"decoration of living room after birth"and"contact with radioactive substances"(P<0.05).There was no significant difference in the complete remission rate of the first course of induction therapy between GG type and GT/TT type children,but the 5-year relapse-free survival rate,5-year event-free survival rate and 5-year overall survival rate of GG type children were significantly lower than those of GT/TT type children(P<0.05).The expression of WNK1 protein in bone marrow cells of children with GG type was significantly lower than that of GT type and TT type(P<0.05).Conclusion:The polymorphism of WNK1 gene rs11611246 locus is related to the susceptibility of children ALL,and has synergistic interaction with some environmental factors,which has certain influence on the prognosis of children.

关 键 词：WNK1 rs11611246 基因多态性 儿童 急性淋巴细胞白血病 

分 类 号：R363.1[医药卫生—病理学]