Association between TP53 polymorphisms and chronic lymphocytic leukemia

W.-J. Zhang, S.-L. Guo, G. Yin, G.-S. Wang, Z.-R. Wang, J. Dong, Q.-R. Li

Department of Hematopathology, Yantaishan Hospital, Yantai, China. houdljining@163.com

---

• Hematology

OBJECTIVE: 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).

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: TP53 polymorphisms are significantly correlated with the occurrence and progression of CLL.

Free PDF Download