Graduate School of Health Sciences, Gunma University, Gunma, Japan.
Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Gunma, Japan.
Eur J Haematol. 2020 Jun;104(6):526-537. doi: 10.1111/ejh.13393. Epub 2020 Mar 4.
Myelodysplastic syndromes (MDS), caused by various genetic mutations in hematopoietic stem cells, are associated with highly variable outcomes. Poly (ADP-ribose) polymerase-1 (PARP1) plays an important role in DNA damage repair and contributes to the progression of several types of cancer. Here, we investigated the impact of PARP1 V762A polymorphism on the susceptibility to and prognosis of MDS.
Samples collected from 105 MDS patients and 202 race-matched healthy controls were subjected to polymerase chain reaction-restriction fragment length polymorphism for genotyping.
The allele and genotype frequencies of PARP1 V762A did not differ between MDS patients and the control group. However, MDS patients with the PARP1 V762A non-AA genotype, which is associated with high gene activity, had shorter overall survival rates (P = .01) than those with the AA genotype. Multivariate analysis of overall survival also revealed PARP1 V762A non-AA genotype as a poor prognostic factor (P = .02). When patients were analyzed according to treatment history, the PARP1 V762A non-AA genotype was only associated with poor survival in patients who had received treatment (P = .02).
PARP1 V762A polymorphism may be an independent prognostic factor for MDS, and a predictive biomarker for MDS treatment.
骨髓增生异常综合征（MDS）是由造血干细胞的各种基因突变引起的，其结局具有高度可变性。聚（ADP-核糖）聚合酶-1（PARP1）在 DNA 损伤修复中起重要作用，并有助于多种类型癌症的进展。在此，我们研究了 PARP1 V762A 多态性对 MDS 的易感性和预后的影响。
对 105 例 MDS 患者和 202 名种族匹配的健康对照者的样本进行聚合酶链反应-限制性片段长度多态性分析以进行基因分型。
PARP1 V762A 的等位基因和基因型频率在 MDS 患者和对照组之间没有差异。然而，PARP1 V762A 非 AA 基因型（与高基因活性相关）的 MDS 患者总生存率较低（P =.01），而非 AA 基因型的患者总生存率较低（P =.02）。总生存的多变量分析也显示 PARP1 V762A 非 AA 基因型是一个不良预后因素。当根据治疗史对患者进行分析时，PARP1 V762A 非 AA 基因型仅与接受治疗的患者的生存不良相关（P =.02）。
PARP1 V762A 多态性可能是 MDS 的独立预后因素，也是 MDS 治疗的预测生物标志物。
