SNP association mapping across the extended major histocompatibility complex and risk of B-cell precursor acute lymphoblastic leukemia in children.
SNP association mapping across the extended major histocompatibility complex and risk of B-cell precursor acute lymphoblastic leukemia in children.
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DOI：
10.1371/journal.pone.0072557
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Buffler PA
中科院分区：
文献类型：
--
作者：
Urayama KY;Chokkalingam AP;Metayer C;Hansen H;May S;Ramsay P;Wiemels JL;Wiencke JK;Trachtenberg E;Thompson P;Ishida Y;Brennan P;Jolly KW;Termuhlen AM;Taylor M;Barcellos LF;Buffler PA
扩展的主要组织相容性复合体（xMHC）是基因组中基因密度最大的区域，并且含有不成比例的大量参与免疫功能的基因。感染在儿童B细胞前体急性淋巴细胞白血病（BCP-ALL）病因中的假定作用表明，xMHC可能对这种疾病的风险做出重要贡献。我们使用一组经过验证的单核苷酸多态性（SNPs），在北方加州儿童白血病研究（NCCLS）中招募的儿童BCP-ALL病例（n=567）与人群对照（n=892）中进行了xMHC约4兆碱基区域的关联作图。对1,145个SNPs进行Logistic回归分析，调整年龄，性别和西班牙裔种族，表明几个SNPs与儿童BCP-ALL之间存在潜在关联。在考虑多重比较后，其中之一包括与rs 9296068相关的统计学显著增加的风险（OR=1.40，95%CI =1.19-1.66，校正p=0.036），位于HLA-DOA附近。滑动窗口单倍型分析鉴定了位于TRIM 27附近的扩展I类区域中的另外的基因座，该基因座由包含rs 1237485、rs3118361和rs 2032502的单倍型标记（校正的全局p=0.046）。我们的研究结果表明，儿童BCP-ALL的易感性受xMHC内遗传变异的影响，并表明至少有两个重要的区域供未来评估。
The extended major histocompatibility complex (xMHC) is the most gene-dense region of the genome and harbors a disproportionately large number of genes involved in immune function. The postulated role of infection in the causation of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) suggests that the xMHC may make an important contribution to the risk of this disease. We conducted association mapping across an approximately 4 megabase region of the xMHC using a validated panel of single nucleotide polymorphisms (SNPs) in childhood BCP-ALL cases (n=567) enrolled in the Northern California Childhood Leukemia Study (NCCLS) compared with population controls (n=892). Logistic regression analyses of 1,145 SNPs, adjusted for age, sex, and Hispanic ethnicity indicated potential associations between several SNPs and childhood BCP-ALL. After accounting for multiple comparisons, one of these included a statistically significant increased risk associated with rs9296068 (OR=1.40, 95% CI=1.19-1.66, corrected p=0.036), located in proximity to HLA-DOA. Sliding window haplotype analysis identified an additional locus located in the extended class I region in proximity to TRIM27 tagged by a haplotype comprising rs1237485, rs3118361, and rs2032502 (corrected global p=0.046). Our findings suggest that susceptibility to childhood BCP-ALL is influenced by genetic variation within the xMHC and indicate at least two important regions for future evaluation.
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影响因子：
4.5
作者：
Barcellos LF;May SL;Ramsay PP;Quach HL;Lane JA;Nititham J;Noble JA;Taylor KE;Quach DL;Chung SA;Kelly JA;Moser KL;Behrens TW;Seldin MF;Thomson G;Harley JB;Gaffney PM;Criswell LA
通讯作者：
Criswell LA
影响因子：
30.8
作者：
Fairfax, Benjamin P.;Makino, Seiko;Radhakrishnan, Jayachandran;Plant, Katharine;Leslie, Stephen;Dilthey, Alexander;Ellis, Peter;Langford, Cordelia;Vannberg, Fredrik O.;Knight, Julian C.
通讯作者：
Knight, Julian C.
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
--
作者：
Do, Thuy N.;Ucisik-Akkaya, Esma;Dorak, M. Tevfik
通讯作者：
Dorak, M. Tevfik
影响因子：
4.4
作者：
Douek, DC;Altmann, DM
通讯作者：
Altmann, DM