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CASP8 基因启动子区域的多态性与中国患者的非霍奇金淋巴瘤无关。

Polymorphisms in the promoter region of the CASP8 gene are not associated with non-Hodgkin's lymphoma in Chinese patients.

机构信息

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.

出版信息

Ann Hematol. 2011 Oct;90(10):1137-44. doi: 10.1007/s00277-011-1265-5. Epub 2011 Jun 2.

Abstract

Caspase-8 (CASP8) involved in apoptosis plays an important role in mediating the normal regulation of cell proliferation, differentiation, inflammation, and homeostasis of multicellular organisms. Genetic polymorphisms, rs3834129 (-/CTTACT) and rs3769821 (T/C), in the promoter region of different CASP8 transcripts, were reported to be associated with genetic susceptibility of multiple cancers and non-Hodgkin's lymphoma (NHL), respectively. To investigate whether these two genetic variants, together with rs113686495 (-/CTGTCATT) which is 50 bp downstream of rs3769821, were associated with NHL in Chinese patients, we genotyped two cohorts of case and control samples from Kunming (case n = 64, control n = 133) and Shanghai (case n = 75, control n = 107). Luciferase assays were further performed to characterize the potential role of different alleles in the promoter region of the CASP8 gene. In contrast to previous studies, we found no difference regarding the genotypes and haplotypes of rs3834129, rs3769821, and rs113686495 between the case and control samples. Luciferase assays of the promoter regions harboring different alleles of these three variants also showed no difference. Our negative results gave no support for an active role for these genetic variants in conferring NHL in Chinese patients.

摘要

半胱氨酸天冬氨酸蛋白酶 8(Caspase-8)参与细胞凋亡,在介导细胞增殖、分化、炎症和多细胞生物内稳态的正常调节中发挥重要作用。在不同的 Caspase-8 转录本启动子区域中,报道了遗传多态性 rs3834129(-/CTTACT)和 rs3769821(T/C)与多种癌症和非霍奇金淋巴瘤(NHL)的遗传易感性相关。为了研究这两个遗传变异体,以及 rs113686495(位于 rs3769821 下游 50bp 的-/CTGTCATT),是否与中国患者的 NHL 相关,我们对来自昆明(病例 n=64,对照 n=133)和上海(病例 n=75,对照 n=107)的两个病例对照样本队列进行了基因分型。进一步进行了荧光素酶检测,以表征不同等位基因在 Caspase-8 基因启动子区域中的潜在作用。与之前的研究不同,我们未发现 rs3834129、rs3769821 和 rs113686495 的基因型和单倍型在病例和对照样本之间存在差异。这些三个变体的不同等位基因的启动子区域的荧光素酶检测也未显示差异。我们的阴性结果不支持这些遗传变异体在赋予中国患者 NHL 方面发挥积极作用。

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