CASP8基因启动子区遗传变异与非霍奇金氏淋巴瘤的易感性研究
文献类型：学位论文
| 作者 | 肖梅生 |
| 学位类别 | 硕士 |
| 答辩日期 | 2011-05 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 姚永刚 |
| 关键词 | CASP8 中国人 非霍奇金氏淋巴瘤 遗传变异 遗传易感性 |
| 其他题名 | Genetic variants in the promoter region of the CASP8 gene on the susceptibility of non-Hodgkin’s lymphoma |
| 学位专业 | 遗传学 |
| 中文摘要 | 非霍奇金氏淋巴瘤（non-Hodgkin’s lymphoma，NHL）是一类淋巴系统恶性肿瘤，它的主要特征是由于淋巴细胞或其前体细胞遗传异常而导致B细胞或者T细胞的恶性增殖。这些遗传上的异常主要包括由于染色体异位而使癌基因或者具有抗凋亡作用的基因异常活化，以及由于基因点突变、插入、缺失和甲基化使抑癌基因和促凋亡因子的失活。 Caspase8（CASP8）是细胞凋亡信号通路中一个上游起始因子，在介导细胞的正常增殖、分化、炎症反应以及维持多细胞有机体的内环境稳态中起到了非常重要的作用。CASP8基因不同转录本的启动子区存在两个遗传多态性位点：rs3834129（CTTACT/-）和rs3769821（T/C），它们分别被报道与多种实体瘤以及NHL的发病风险相关。为了研究这两个遗传变异位点是否与我国NHL患者发病相关，我们收集了139份NHL患者血液或骨髓样本和240份普通对照血液样本，采用病例-对照的方法对包括rs3769821下游50bp处另一个位点rs113686495（CTGTCATT/-）在内的三个位点进行了基因分型和关联性分析。和前人报道结果不一致的是，我们未在病例和对照之间观察到这三个多态性位点（rs3834129，rs3769821和rs113686495）的等位基因频率、基因型和单倍型存在显著性的统计学差异。进一步用荧光素酶实验分析了不同等位基因在CASP8基因启动子区的潜在作用，结果显示对于启动子区这三个遗传变异，不同的等位基因对荧光素酶的表达没有显著的影响。我们的实验结果提示CASP8基因启动子区这三个遗传变异位点很可能与我国NHL患者的易感性无关。 本研究首次在我国人群中利用病例-对照方法究了CASP8基因启动子区三个多态性位点与NHL发病的相关性，结果显示这三个遗传变异和NHL患者的发病没有相关性，并且功能实验验证了这三个变异位点不影响CASP8基因的表达。本研究为CASP8基因与NHL发病以及NHL的遗传易感性研究提供了一些基础数据。 |
| 英文摘要 | Non-Hodgkin’s lymphoma (NHL) is a group of heterogeneous malignancies of the lymphatic system which is characterized by genetic abnormalities of lymphoid cells and/or their precursors, leading to malignant expansion of B or T cells. These genetic abnormalities include activation of oncogenes and antiapoptosis genes by chromosomal translocations, as well as, the inactivation of tumor suppressor genes and apoptosis genes due to point mutations, insertion, deletion and/or methylation. Caspase8 (CASP8), which is an initiative caspase in the apoptosis pathway, plays an important role in mediating the normal regulation of cell proliferation, differentiation, inflammation and homeostasis of multi-cellular organisms. Genetic polymorphisms rs3834129 (CTTACT/-) and rs3769821 (T/C) in the promoter region of different CASP8 transcriptswere reported to be associated with genetic susceptibility of multiple cancers and NHL, respectively. To investigate whether these two genetic variants, together with rs113686495 (CTGTCATT/-) which is 50bp downstream of rs3769821, were associated with genetic susceptibility to NHL in Chinese patients, we collected a total of 379 samples (cases, n = 139 and controls, n = 240) and performed a population based case-control study. However, in contrast to previous reports, we found no significant difference regarding the allele frequencies, genotypes and haplotypes of rs3834129, rs3769821 and rs113686495 between the case and control samples. Luciferase assays were further performed to characterize the potential role of different alleles in the promoter region of the CASP8 gene. Luciferase assays of the promoter regions harboring different alleles of these three variants also showed no statistically significant difference. Our results suggest that there is no active role of these three genetic variants in the promoter region of CASP8 in conferring the susceptibility to NHL in Chinese patients. To our knowledge, there is no systematic study to investigate the relationship between genetic polymorphisms in the promoter regions of CASP8 gene and the susceptibility to NHL in Chinese population. Our current results suggested that there were no association between these genetic variants and NHL. Further functional experiments showed that the expression of the CASP8 gene was not influenced by these genetic variants. This study provides some preliminary data for understanding the role of CASP8 in the pathogenesis of NHL and the investigation of genetic susceptibility to NHL. |
| 语种 | 中文 |
| 公开日期 | 2013-04-23 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7380]  |
| 专题 | 昆明动物研究所_重大疾病机理的遗传学 |
| 推荐引用方式 GB/T 7714 | 肖梅生. CASP8基因启动子区遗传变异与非霍奇金氏淋巴瘤的易感性研究[D]. 北京. 中国科学院研究生院. 2011. |
入库方式： OAI收割
来源：昆明动物研究所
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