Search on chromosome 17 centromere reveals TNFRSF13B as a susceptibility gene for intracranial aneurysm -: A preliminary study
Search on chromosome 17 centromere reveals TNFRSF13B as a susceptibility gene for intracranial aneurysm -: A preliminary study
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DOI：
10.1161/circulationaha.105.579326
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发表时间：
2006-04-25
期刊：
影响因子：
37.8
通讯作者：
Koizumi, A
中科院分区：
文献类型：
--
作者：
Inoue, K;Mineharu, Y;Koizumi, A
背景：我们之前的研究表明颅内动脉瘤（IAs）与17号染色体有显著的联系。方法和结果：从D17S1857和D17S1871之间的108个基因中筛选出9个基因（TNFRSF13B、M-RIP、COPS3、RAII、SREBF1、GRAP、MAPK7、MFAP4和AKAP10），剔除99个假基因、假设基因或特征良好但不可能与IA相关的基因。对58例（29例家系先证者和29例无关非家系病例）的所有编码区和调控区进行直接测序。仅在TNFRSF13B、K154X和c. 585 ~ 586insA外显子4中发现有害变化。在304例无关病例和332例对照中进一步研究IA与TNFRSF13B的相关性。罕见的非同义改变，剪接受体位点改变和帧移位，在不相关的病例中（2.3%，608例中14例）比对照组（0.8%，664例中5例，P = 0.035）更常见。在一个不相关的病例对照队列中使用单核苷酸多态性的关联研究显示，校正协变量后，与主要单倍型相比，保护性单倍型（优势比0.69,95%置信区间0.52 ~ 0.92,P = 0.012）。结论：我们认为TNFRSF13B是IA的易感基因之一。
Background: Our previous studies have shown a significant linkage of intracranial aneurysms (IAs) to chromosome 17.Methods and Results: Nine genes (TNFRSF13B, M-RIP, COPS3, RAII, SREBF1, GRAP, MAPK7, MFAP4, and AKAP10) were selected from 108 genes that are located between D17S1857 and D17S1871 by excluding 99 genes that were pseudogenes, hypothetical genes, or well-characterized genes but not likely associated with IA. Direct sequencing of all coding and regulatory regions in 58 cases (29 pedigree probands and 29 unrelated nonpedigree cases) was performed. Deleterious changes were found only in TNFRSF13B, K154X, and c. 585 to 586insA in exon4. The association of IA with TNFRSF13B was further studied in 304 unrelated cases and 332 control subjects. Rare nonsynonymous changes, a splicing acceptor site change and a frame shift, were found in unrelated cases (2.3%; 14 of 608) more frequently than in control subjects (0.8%; 5 of 664; P = 0.035). The association study using single-nucleotide polymorphisms in an unrelated case-control cohort revealed a protective haplotype (odds ratio 0.69, 95% confidence interval 0.52 to 0.92, P = 0.012) compared with the major haplotype after adjustment for covariates.Conclusions: We propose that TNFRSF13B is one of the susceptibility genes for IA.