Department of Medical Genetics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania.
Center for Advanced Medical and Pharmaceutical Research, Genetics Laboratory, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania.
Int J Mol Sci. 2024 Feb 1;25(3):1799. doi: 10.3390/ijms25031799.
The aim of the current study was to assess the associations between genetic risk factors (such as the mutational status of the gene and polymorphisms of the and genes) and CLL risk, prognosis, and overall survival. Another goal of this study was to evaluate the multivariate effect of the combination of multiple genetic risk factors (mutational status of the gene, somatic mutations, DNA CNVs, and cytokine SNPs) on the clinical characteristics and survival of patients. A total of 125 CLL patients and 239 healthy controls were included for comparative SNP analysis. (rs1800896 and rs1800872) and (rs361525 and rs1800750) SNPs and haplotypes were not associated with CLL risk. The absence of hypermutation in the gene was shown to be of important prognostic value, being associated with short OS. Further individual risk factors for short OS were an age above 65 years at diagnosis and the presence of somatic mutations and/or CNVs. In our multivariable analysis, the presence of somatic mutations and the rs1800872 variant allele, and the association of CNVs with the rs1800896 variant allele, were identified as risk factors for short OS. Moreover, the OS in unmutated patients was additionally affected (decreased) by the presence of CNVs and/or somatic mutations. Similarly, rs1800896 modulated the OS in unmutated patients with CNVs.
本研究旨在评估遗传风险因素(如 基因的突变状态和 基因和 基因的多态性)与 CLL 风险、预后和总生存期之间的关联。本研究的另一个目的是评估多个遗传风险因素( 基因的突变状态、体细胞突变、DNA CNV 和细胞因子 SNPs)组合对患者临床特征和生存的多变量影响。共纳入 125 例 CLL 患者和 239 例健康对照进行比较 SNP 分析。 (rs1800896 和 rs1800872)和 (rs361525 和 rs1800750)SNP 及其单倍型与 CLL 风险无关。 基因中不存在超突变被证明具有重要的预后价值,与 OS 较短有关。进一步导致 OS 较短的个体危险因素是诊断时年龄大于 65 岁以及存在体细胞突变和/或 CNV。在我们的多变量分析中,体细胞突变的存在和 rs1800872 变体等位基因,以及 CNV 与 rs1800896 变体等位基因的关联,被确定为 OS 较短的危险因素。此外,未突变的 患者的 OS 还受到 CNV 和/或体细胞突变的影响(降低)。同样,rs1800896 调节了携带 CNV 的未突变的 患者的 OS。