Polymorphisms in innate immunity genes and risk of childhood leukemia.
Polymorphisms in innate immunity genes and risk of childhood leukemia.
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DOI：
10.1016/j.humimm.2010.04.004
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发表时间：
2010-07
期刊：
影响因子：
2.7
通讯作者：
Kang D
中科院分区：
文献类型：
--
作者：
Han S;Lan Q;Park AK;Lee KM;Park SK;Ahn HS;Shin HY;Kang HJ;Koo HH;Seo JJ;Choi JE;Ahn YO;Chanock SJ;Kim H;Rothman N;Kang D
为了评估先天免疫中的候选基因是否与儿童白血病相关，我们对203个与先天免疫相关的基因中的1536个单核苷酸多态性（SNP）进行了一项相关性研究。
2003年至2006年期间，从首尔的三家教学医院招募了年龄在0到18岁的儿童白血病新发病例（n = 136）。非癌症对照（n = 140）按照年龄和性别与病例进行频率匹配。由经过培训的调查员使用结构化问卷收集儿童及其父母的特征信息。候选基因是根据SNP数据库（癌症基因组解剖计划（CGAP）和SNP500数据库）选择的，并且使用金标准（Illumina）寡核苷酸池分析（OPA）进行基因型检测。采用错误发现率（FDR）、置换检验和单倍型分析来确定与儿童白血病显著相关的SNP。儿童白血病风险以调整了年龄、性别和出生体重的比值比（OR）和95%置信区间（CI）来估计。
13个基因（LMAN1、TLR4、STAT4、CCR9、MBP、ZP1、C8B、XDH、C7、C1QG、FGF2、LOC390183和STAT6）中的14个SNP与儿童白血病风险显著相关（FDR p值<0.05）。特别是，LMAN1 rs1127220、TLR4 rs11536897、STAT4 rs13020076、CCR9 rs1471962和MBP rs10514234在5000次置换检验中具有显著性（置换p值<0.05）。与儿童白血病风险最显著相关的是位于蛋白质编码区的LMAN1 rs1127220，这一发现也得到了单倍型分析的支持。
许多与先天免疫相关的基因与儿童白血病有关，这表明先天免疫系统与儿童白血病的发生之间可能存在联系。
To evaluate whether candidate genes in innate immunity are associated with childhood leukemia, we conducted an association study with the 1,536 SNPs in 203 genes related to innate immunity. Incident childhood leukemia cases (n=136) aged from 0 to 18 were recruited from three teaching hospitals in Seoul between 2003 and 2006. Non-cancer controls (n=140) were frequency-matched to cases by age and gender. The information on the characteristics of children and their parents were collected by trained interviewers using structured questionnaire. Candidate genes were selected based on SNP databases (CGAP and SNP500 database), and genotype assay was performed using GoldenGate (Illumina) oligonucleotide pool assay (OPA). False discovery rate (FDR), permutation test, and haplotype analyses were used to identify the SNP with significant association with childhood leukemia. Childhood leukemia risk was estimated as ORs and 95% CIs adjusted for age, gender and birth weight. Fourteen SNPs in 13 genes (LMAN1, TLR4, STAT4, CCR9, MBP, ZP1, C8B, XDH, C7, C1QG, FGF2, LOC390183, and STAT6) were significantly associated with childhood leukemia risk (FDR p-values <0.05). In particular, LMAN1 rs1127220, TLR4 rs11536897, STAT4 rs13020076, CCR9 rs1471962, and MBP rs10514234 were significant in 5,000 permutation tests (Permutation p-value <0.05). The most significant association with childhood leukemia risk was for the LMAN1 rs1127220 that is in the protein-coding region, this finding was also supported by haplotype analysis. A number of innate immunity related genes are associated with childhood leukemia, suggesting possible links between the innate immunity system and development of the childhood leukemia.
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DOI：
10.1073/pnas.93.17.8977
发表时间：
1996-08-20
影响因子：
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作者：
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