Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules(益髓生血颗粒)

• 来源期刊: 中国结合医学杂志（英文版）
• 年，卷（期）: 2019,（7）
• 页码范围: 490-496
• 页数: 7页
• 语种: 英文
• DOI: 10.1007/s11655-018-2777-9

摘要

Objective:To examine the clinical effects of Yisui Shengxue Granules（益髓生血颗粒）in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels.Methods:A randomized placebo-controlled double-blinded trial was conducted.Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group,20 patients in each group.The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group (12 g/bag,3 times a day) during a 3-month intervention.Before and after 1,2,and 3 months of treatment,peripheral intravenous blood was sampled,and blood parameters such as hemoglobin (Hb),red blood cells (RBCs),reticulocytes (Ret),and fetal hemoglobin (HbF) were analyzed.Mononuclear cells from 5 patients,who showed an obvious treatment effect,were isolated by density gradient centrifugation.DNA methylation was analyzed using an Affymetrix USA GeneChip Human Promoter 1.0 Array and Input-promoter 1.0.Results:Compared with pre-treatment,there was an obvious increase in Hb and RBCs counts after 1,2,and 3 months in the experiment group (P＜0.01 or P＜0.05).Meanwhile,HbF increased from the 2nd to the 3rd month (P＜0.05).In the control group,Hb and RBCs showed no obvioas change.After 3-month treatment,DNA methylation results from 5 patients revealed that there were 24 hypomethylated genes and 3,685 hypermethylated genes compared with pre-treatment.Genes of insulin-like growth factor 1 receptor (IGF1 R) and Janus kinase 3 (JAK3)revealed the most relations with other genes (degree:21) and genes of 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma 2 (PLCG2) and mitogen-activated protein kinase 10 (MAPK10) showed a stronger intermediary role (betweenness centrality=0.04).Conclusions:JAK3 and MAPK10 are two key genes in bone marrow and the lymphatic system,and JAK3 is likely to be related to hematopoietic cytokines in the process of early hematopoiesis.(Registration No.NCT01549080)