Department of Hematopathology, Yantaishan Hospital, Yantai, China.
Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12073-12079. doi: 10.26355/eurrev_202012_23996.
The aim of this study was to explore the association between TP53 gene polymorphisms (rs8068934 A>G and rs218698 C>T) and chronic lymphocytic leukemia (CLL).
CLL patients who received treatment in our hospital were enrolled in this study as the disease group. Meanwhile, healthy subjects were taken as the control group. Peripheral blood samples were collected to detect TP53 gene polymorphisms at rs8068934 and rs218698, and the haplotype analysis was performed. The expression of TP53 was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Furthermore, the survival conditions were analyzed.
The allele distribution at rs8068934 (p=0.046) and rs218698 (p=0.028) of TP53 gene was different between control group and disease group. A allele frequency at rs8068934 and T allele frequency at rs218698 were significantly higher in disease group (p<0.05). The genotype distribution at rs218698 of TP53 gene in disease group was also different from that in control group (p=0.038). The results demonstrated that CC genotype frequency in disease group was significantly lower than that in control group (p<0.05). Besides, the distribution of dominant model at rs8068934 (p=0.042) and recessive model at rs218698 (p=0.033) in disease group exhibited remarkable differences from control group, in which AA+AG frequency (dominant model) at rs8068934 and CC+CT frequency (recessive model) at rs218698 in disease group were significantly higher. Meanwhile, the distribution of AT (p=0.029) and GC (p=0.007) haplotypes at rs8068934 and rs218698 in disease group was evidently different from that in control group. The results indicated that disease group showed significantly higher frequency of AT haplotype and lower frequency of GC haplotype (p<0.05). Moreover, TP53 gene polymorphisms at rs8068934 were significantly associated with the levels of white blood cells (WBC) (p=0.000) and platelets (PLT) (p=0.035). Patients with GG genotype had significantly higher level of WBC, while those with AG genotype showed significantly lower level of PLT (p<0.05). TP53 gene polymorphisms at rs218698 were associated with the level of red blood cells (RBC) (p=0.000). Patients with CT genotype had a remarkably lower level of RBC (p<0.05). There were significant correlations of TP53 gene polymorphisms at rs8068934 (p=0.000) and rs218698 (p=0.000) with the expression of TP53. The expression of TP53 was lower in people with AA genotype at rs8068934 but higher in people with TT genotype at rs218698 (p<0.05). Furthermore, TP53 gene polymorphisms at rs8068934 (p=0.000) and rs218698 (p=0.000) were markedly associated with patients' survival.
TP53 polymorphisms are significantly correlated with the occurrence and progression of CLL.
本研究旨在探讨 TP53 基因多态性(rs8068934 A>G 和 rs218698 C>T)与慢性淋巴细胞白血病(CLL)之间的关系。
将在我院接受治疗的 CLL 患者纳入疾病组,同时选择健康受试者作为对照组。采集外周血样本,检测 TP53 基因 rs8068934 和 rs218698 的多态性,并进行单倍型分析。采用逆转录定量聚合酶链反应(RT-qPCR)检测 TP53 的表达。此外,还分析了患者的生存情况。
TP53 基因 rs8068934(p=0.046)和 rs218698(p=0.028)的等位基因分布在对照组和疾病组之间存在差异。疾病组 A 等位基因频率和 T 等位基因频率明显升高(p<0.05)。TP53 基因 rs218698 的基因型分布在疾病组也与对照组不同(p=0.038)。结果表明,疾病组 CC 基因型频率明显低于对照组(p<0.05)。此外,rs8068934 的显性模型(p=0.042)和 rs218698 的隐性模型(p=0.033)在疾病组的分布也存在显著差异,rs8068934 的 AA+AG 频率(显性模型)和 rs218698 的 CC+CT 频率(隐性模型)在疾病组明显升高。同时,rs8068934 和 rs218698 处 AT(p=0.029)和 GC(p=0.007)单倍型的分布在疾病组与对照组之间也存在明显差异。结果表明,疾病组 AT 单倍型的频率明显升高,GC 单倍型的频率明显降低(p<0.05)。此外,TP53 基因 rs8068934 的多态性与白细胞(WBC)水平(p=0.000)和血小板(PLT)水平(p=0.035)显著相关。GG 基因型患者的 WBC 水平明显升高,而 AG 基因型患者的 PLT 水平明显降低(p<0.05)。TP53 基因 rs218698 的多态性与红细胞(RBC)水平(p=0.000)相关。CT 基因型患者的 RBC 水平明显降低(p<0.05)。TP53 基因 rs8068934(p=0.000)和 rs218698(p=0.000)的多态性与 TP53 的表达显著相关。rs8068934 处 AA 基因型的 TP53 表达降低,但 rs218698 处 TT 基因型的 TP53 表达升高(p<0.05)。此外,TP53 基因 rs8068934(p=0.000)和 rs218698(p=0.000)的多态性与患者的生存明显相关。
TP53 多态性与 CLL 的发生和进展显著相关。