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

作　　者：CHENG Yan-ling ZHANG Xin-hua SUN Yu-wen WANG Wen-juan HUANG Jie CHU Na-li FANG Su-ping WU Zhi-kui 

机构地区：[1]Molecular Biology Labaratory, South of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing (102618), China [2]Department of Hematology, 303rd Hospital of People's Liberatory Army, Nanning (530021), China [3]Molecular Biology Laboratory of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing (100053), China [4]School of Traditional Chinese Medicine, Capital Medical University, Beijing (100069), China

出　　处：《Chinese Journal of Integrative Medicine》2019年第7期490-496,共7页中国结合医学杂志（英文版）

基　　金：Supported by the National Basic Research Program of China(No.2010CB530406);National Natural Science Foundation of China(No.81173167);the Natural Science Foundation of Guangxi(No.2012GXNSFAA053156)

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 2 nd to the 3 rd 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. NCTObjective: 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 2 nd to the 3 rd 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. NCT

关 键 词：Β-THALASSEMIA Yisui Shengxue GRANULE Chinese medicine DNA-METHYLATION 

分 类 号：R259[医药卫生—中西医结合]