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Abstract：
Background and objectives: Acute myeloid leukemia (AML) is a hematological malignancy characterized by uncontrolled proliferation of immature myeloid cells. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are essential for controlling anti-tumor immune responses. This study aims to explore the correlation between specific genetic variations (SNPs) in the PDCD1 (rs2227981) and LAG3 (rs12313899) genes and the likelihood of developing AML in the Saudi population. Material and methods: total of 98 Saudi AML patients and 131 healthy controls were genotyped for the PDCD1 rs2227981 and LAG3 rs12313899 polymorphisms using TaqMan genotyping assays. A logistic regression analysis was conducted to evaluate the relationship between the SNPs and AML risk using several genetic models. Results: The results revealed a significant association between the PDCD1 rs2227981 polymorphism and increased AML risk. In AML patients, the frequency of the G allele was considerably greater than in healthy controls (OR = 1.93, 95% CI: 1.31-2.81, p = 0.00080). The GG and AG genotypes were associated with a very high risk of developing AML (p < 0.0001). In contrast, no significant association was observed between the LAG3 rs12313899 polymorphism and AML risk in the studied population. In silico analysis of gene expression profiles from public databases suggested the potential impact of PDCD1 expression levels on the overall survival of AML patients. Conclusions: This study provides evidence for the association of the PDCD1 rs2227981 polymorphism with an increased risk for AML in the Saudi population.
摘要：
背景和目的：急性髓系白血病（AML）是一种血液系统恶性肿瘤，其特征是未成熟骨髓细胞的增殖不受控制。免疫检查点分子如程序性细胞死亡蛋白1(PD-1)和淋巴细胞活化基因-3(LAG-3)对于控制抗肿瘤免疫应答是必不可少的。这项研究旨在探讨PDCD1（rs2227981）和LAG3（rs12313899）基因中特定遗传变异（SNPs）之间的相关性以及在沙特人群中发生AML的可能性。材料和方法：使用TaqMan基因分型分析，对98名沙特AML患者和131名健康对照进行了PDCD1rs2227981和LAG3rs12313899多态性的基因分型。使用几种遗传模型进行逻辑回归分析以评估SNP与AML风险之间的关系。结果：结果显示PDCD1rs2227981多态性与AML风险增加之间存在显著关联。在AML患者中，G等位基因频率显著高于健康对照组(OR=1.93,95%CI:1.31-2.81,p=0.00080).GG和AG基因型与发展AML的非常高的风险相关(p<0.0001)。相比之下,在研究人群中,LAG3rs12313899多态性与AML风险之间未观察到显著关联.来自公共数据库的基因表达谱的计算机模拟分析提示PDCD1表达水平对AML患者的总体存活的潜在影响。结论：本研究提供了PDCD1rs2227981多态性与沙特阿拉伯人群AML风险增加相关的证据。
