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编码 TLRs、NLRs 和 RLRs 的基因多态性与急性髓系白血病患者的临床参数相关。

Polymorphisms in the Genes Coding for TLRs, NLRs and RLRs Are Associated with Clinical Parameters of Patients with Acute Myeloid Leukemia.

机构信息

Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation of Wroclaw Medical University, 50-367 Wroclaw, Poland.

Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.

出版信息

Int J Mol Sci. 2022 Aug 24;23(17):9593. doi: 10.3390/ijms23179593.

Abstract

Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) are major elements of the innate immune system that recognize pathogen-associated molecular patterns. Single-nucleotide polymorphisms (SNPs) in the TLR, NLR, and RLR genes may lead to an imbalance in the production of pro- and anti-inflammatory cytokines, changes in susceptibility to infections, the development of diseases, and carcinogenesis. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. We retrospectively analyzed 90 AML patients. We investigated the effect of fifteen SNPs located in the genes coding for RLR1 (rs9695310, rs10738889, rs10813831), NOD1 (rs2075820, rs6958571), NOD2 (rs2066845, rs2066847, rs2066844), TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790), and TLR9 (rs187084, rs5743836). We observed that rs4986791, rs5743836, and rs2066847 were associated with CRP levels, while rs10738889 was associated with LDH level. Furthermore, we found rs5743305 to be more common in patients with infections. We also found rs187084 to be associated with more favorable risk, and RLR-1 rs9695310 with higher age at diagnosis. In conclusion, the current study showed that SNPs in the genes encoding TLRs, NLRs, and RLRs may be potential biomarkers in patients with AML.

摘要

Toll 样受体 (TLRs)、NOD 样受体 (NLRs) 和 RIG-I 样受体 (RLRs) 是识别病原体相关分子模式的固有免疫系统的主要元素。TLR、NLR 和 RLR 基因中的单核苷酸多态性 (SNP) 可能导致促炎和抗炎细胞因子的产生失衡、对感染的易感性改变、疾病的发展和癌变。急性髓系白血病 (AML) 是一种骨髓恶性肿瘤,其特征是转化的髓样前体不受控制地增殖。我们回顾性分析了 90 例 AML 患者。我们研究了位于编码 RLR1(rs9695310、rs10738889、rs10813831)、NOD1(rs2075820、rs6958571)、NOD2(rs2066845、rs2066847、rs2066844)、TLR3(rs5743305、rs3775296、3775291)、TLR4(rs4986791、rs4986790)和 TLR9(rs187084、rs5743836) 的 15 个 SNP 的影响。我们观察到 rs4986791、rs5743836 和 rs2066847 与 CRP 水平相关,而 rs10738889 与 LDH 水平相关。此外,我们发现 rs5743305 在感染患者中更为常见。我们还发现 rs187084 与更有利的风险相关,而 RLR-1 rs9695310 与诊断时的年龄更高相关。总之,本研究表明,编码 TLRs、NLRs 和 RLRs 的基因中的 SNP 可能是 AML 患者的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d2/9455872/b596ff912030/ijms-23-09593-g001.jpg

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