Nursal Ayse Feyda, Pehlivan Mustafa, Sahin Handan Haydaroğlu, Pehlivan Sacide
1 Department of Medical Genetics, Faculty of Medicine, Giresun University , Giresun, Turkey .
2 Department of Hematology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
Genet Test Mol Biomarkers. 2016 Sep;20(9):544-51. doi: 10.1089/gtmb.2016.0036. Epub 2016 Aug 3.
It has been suggested that cytokine dysregulation could be associated with pathogenesis, progression, and survival in acute myeloid leukemia (AML). The purpose of this study was to evaluate the relationship of functional single-nucleotide polymorphisms (SNPs) in cytokine gene and cytokine expression levels with AML.
Peripheral blood samples were collected from 42 patients with AML and 85 healthy individuals. Eight SNPs in five cytokine genes, including interleukin 6 (IL-6), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and transforming growth factor-β 1 (TGF-β1), were analyzed using the polymerase chain reaction sequence-specific primer method.
We found that the frequencies of the TNF-α (-308) GG genotype and G allele were significantly higher in the patients with AML compared to the healthy control group (p = 0.020 and 0.014). The AML patients had significantly lower frequencies of the CC genotype and C allele of the IL-10 (-819 SNP), the G allele of the IL-10 (-1082 SNP), the CC genotype and C allele of the IL-10 (-592 SNP), and the codon 25 GC genotype of TGF-β1, (p = 0.024, p = 0.012, p = 0.038, p = 0.024, p = 0.012, p = 0.028, respectively). However, no significant differences were found between AML and healthy control groups with respect to the distributions of genotypes in IL-6, IFN-γ, IL-10 (-1082), TGF-β1 (codon 10), and haplotypes of IL-10, TGF-β1 gene.
Our results suggest that functional variants of the TNF-α, IL-10, and TGF-β1 genes may have a significant association with the etiopathogenesis of AML. Further studies with larger groups and different ethnicities are needed to determine the impact of cytokine variants on the risk of developing AML.
有人提出细胞因子失调可能与急性髓系白血病(AML)的发病机制、进展及生存相关。本研究旨在评估细胞因子基因中的功能性单核苷酸多态性(SNP)及细胞因子表达水平与AML的关系。
采集42例AML患者及85例健康个体的外周血样本。采用聚合酶链反应序列特异性引物法分析5种细胞因子基因中的8个SNP,包括白细胞介素6(IL-6)、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)和转化生长因子-β1(TGF-β1)。
我们发现,与健康对照组相比,AML患者中TNF-α(-308)GG基因型和G等位基因的频率显著更高(p = 0.020和0.014)。AML患者中IL-10(-819 SNP)的CC基因型和C等位基因、IL-10(-1082 SNP)的G等位基因、IL-10(-592 SNP)的CC基因型和C等位基因以及TGF-β1密码子25的GC基因型的频率显著更低(分别为p = 0.024、p = 0.012、p = 0.038、p = 0.024、p = 0.012、p = 0.028)。然而,在IL-6、IFN-γ、IL-10(-1082)、TGF-β1(密码子10)的基因型分布以及IL-10、TGF-β1基因单倍型方面,AML组与健康对照组之间未发现显著差异。
我们的结果表明,TNF-α、IL-10和TGF-β1基因的功能性变异可能与AML的病因发病机制存在显著关联。需要进一步开展更大样本量和不同种族的研究,以确定细胞因子变异对发生AML风险的影响。