Qasim Mohammed Maryam, Hussein Alwan Ali, Amer Almukhtar Asmaa, Kareem Aneed Al-Saedi Mohanad
Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq.
Iraqi Center for Cancer and Medical Genetics Research, Baghdad, Iraq.
Cytokine. 2024 Oct;182:156730. doi: 10.1016/j.cyto.2024.156730. Epub 2024 Aug 11.
Acute myeloid leukemia (AML) is one of the most common and fatal malignancies that affect adults, which can quickly become aggressive if left untreated, and leukemia cells invade the bone marrow. TLR-9 is an innate immune cell receptor sensitive to various PAMPs and encoded by the TLR-9 gene. As is often known, genetic polymorphisms in any gene can help the development of the disease, and these three polymorphisms, rs187084, rs5743836, and rs352140 of TLR-9, have been studied in many different cancer disorders. Therefore, this study aimed to discover the multiple forms of a TLR-9 gene in a sample of Iraqi AML patients. A total of 120 participants in a case-control study were enrolled in the current study. Using CBC, some hematological parameters were evaluated, and the serum level of TLR-9 was assessed using the ELISA technique. DNA was extracted directly from blood, and a high-resolution melting (HRM) analysis was then carried out. The results revealed a significant difference in some blood parameters among patients and healthy control, while WBC and lymphocytes were without an evident difference between the two groups of the current investigation. The serum concentration of TLR-9 showed an elevated level in patients (P value < 0.01). Nonetheless, this increase was not affected by the genotype patterns of polymorphisms. According to the P-value, there was a significant difference in wild genotypes of the three polymorphisms (rs187084, rs5743836, and rs352140). At the same time, the odds ratio revealed the association with the disease as a protective factor. In contrast, there was a significant difference in the heterozygous and mutant genotypes of TLR-9 polymorphisms, though the odds ratio confirmed the association with the AML as a risk factor. The results of rs352140 were compatible with H.W.E since there were no significant differences between the observed and expected values for either patients or healthy controls. In contrast, the result of rs5743836 was not consistent with the HWE. Furthermore, although it corresponds with the healthy one, the finding of rs187084 conflicted with H.W.E. in the patient group. In conclusion, High serum levels of TLR-9 in patients could act as biomarkers for AML. The TLR-9 gene polymorphisms (rs187084, rs5743836, and rs352140) have been linked to an increased risk of AML and may impact the disease progression in the Iraqi population.
急性髓系白血病（AML）是影响成年人的最常见且致命的恶性肿瘤之一，如果不进行治疗，它会迅速恶化，白血病细胞会侵入骨髓。TLR - 9是一种对多种病原体相关分子模式敏感的天然免疫细胞受体，由TLR - 9基因编码。众所周知，任何基因中的遗传多态性都可能促进疾病的发展，并且在许多不同的癌症疾病中都对TLR - 9的这三种多态性rs187084、rs5743836和rs352140进行了研究。因此，本研究旨在发现伊拉克AML患者样本中TLR - 9基因的多种形式。本研究共纳入了120名病例对照研究的参与者。通过全血细胞计数（CBC）评估了一些血液学参数，并使用酶联免疫吸附测定（ELISA）技术评估了TLR - 9的血清水平。直接从血液中提取DNA，然后进行高分辨率熔解（HRM）分析。结果显示，患者与健康对照之间的一些血液参数存在显著差异，而白细胞（WBC）和淋巴细胞在本研究的两组之间没有明显差异。患者的TLR - 9血清浓度显示升高（P值<0.01）。然而，这种升高不受多态性基因型模式的影响。根据P值，三种多态性（rs187084、rs5743836和rs352140）的野生基因型存在显著差异。同时，优势比显示其与疾病的关联为保护因素。相比之下，TLR - 9多态性的杂合子和突变基因型存在显著差异，尽管优势比证实其与AML的关联为危险因素。rs352140的结果符合哈迪 - 温伯格平衡（H.W.E），因为患者或健康对照的观察值与预期值之间没有显著差异。相比之下，rs5743836的结果与哈迪 - 温伯格平衡不一致。此外，尽管rs187084的结果与健康组相符，但其在患者组中的发现与哈迪 - 温伯格平衡相冲突。总之，患者中TLR - 9的高血清水平可作为AML的生物标志物。TLR - 9基因多态性（rs187084、rs5743836和rs352140）与AML风险增加有关，可能影响伊拉克人群的疾病进展。
