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慢性髓性白血病患者中NLRP3炎性小体的基因多态性及表达谱

The genetic polymorphism and expression profiles of NLRP3 inflammasome in patients with chronic myeloid leukemia.

作者信息

Zhang Amin, Yu Jie, Yan Shuxin, Zhao Xia, Chen Chen, Zhou Ying, Zhao Xueyun, Hua Mingqiang, Wang Ruiqing, Zhang Chen, Zhong Chaoqin, He Na, Ji Chunyan, Ma Daoxin

机构信息

Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, PR China.

Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, PR China.

出版信息

Hum Immunol. 2018 Jan;79(1):57-62. doi: 10.1016/j.humimm.2017.10.013. Epub 2017 Oct 31.

Abstract

NLRP3 inflammasome has been recently reported as an important risk factor in the development of cancer. But the relationship between polymorphisms of NLRP3 inflammasome related genes and chronic myeloid leukemia (CML) is rarely reported. Therefore, the aim of the present study was to investigate the association of five genetic polymorphisms (NLRP3, IL-1β, IL-18, CARD8 and NF-κB) in 267 CML patients and 344 healthy controls. We found that the AT genotype of CARD8 (rs2043211) was significantly higher compared to TT genotype in high and intermediate risk CML patients. IL-1β (rs16944) polymorphism in early molecular response at 6 months was marginally different, with more GG and less AA genotype in BCR-ABL >1% group. IL-18 (rs1946518) polymorphism was significantly different with more GG genotype in BCR-ABL >1% group at 6 months. We also demonstrated that WBC count of newly diagnosed patients carrying AG genotype was significantly higher than that of GG or AA genotype of IL-1β (rs16944). The onset age of patients carrying ins/ins genotype of NF-κB (rs28362491) was significantly older than that of ins/del and del/del genotype. Moreover, IL-1β or NLRP3 mRNA expression was decreased and IL-18 mRNA expression was increased significantly in CML patients compared with controls. In conclusion, the genetic polymorphisms of NLRP3 inflammasome may be served as potential predictors for CML.

摘要

NLRP3炎性小体最近被报道为癌症发生发展的一个重要危险因素。但NLRP3炎性小体相关基因多态性与慢性髓系白血病(CML)之间的关系鲜有报道。因此,本研究的目的是调查267例CML患者和344例健康对照中5种基因多态性(NLRP3、IL-1β、IL-18、CARD8和NF-κB)的相关性。我们发现,在高危和中危CML患者中,CARD8(rs2043211)的AT基因型显著高于TT基因型。6个月时早期分子反应中的IL-1β(rs16944)多态性存在微小差异,在BCR-ABL>1%组中,GG基因型更多,AA基因型更少。IL-18(rs1946518)多态性存在显著差异,在6个月时BCR-ABL>1%组中GG基因型更多。我们还证明,携带IL-1β(rs16944)AG基因型的新诊断患者的白细胞计数显著高于GG或AA基因型患者。携带NF-κB(rs28362491)ins/ins基因型患者的发病年龄显著高于ins/del和del/del基因型患者。此外,与对照组相比,CML患者中IL-1β或NLRP3 mRNA表达降低,IL-18 mRNA表达显著升高。总之,NLRP3炎性小体的基因多态性可能作为CML的潜在预测指标。

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