title: Association of nitric oxide synthase 3 (NOS3) 894 G>T polymorphism with prognostic outcomes of anthracycline in Chinese patients with acute myeloid leukaemia.
abstract: The aim of the present study was to investigate the influence of the nitric oxide synthase 3 (NOS3) 894 G>T polymorphism on prognostic outcomes of anthracycline in Chinese patients with de novo intermediate-risk acute myeloid leukaemia (AML) and to examine the gene expression level in relation to genetic variation. In all, 225 Chinese patients with intermediate-risk AML (at the complete remission stage) treated with anthracycline were enrolled in the study. The 894 G>T polymorphism of the NOS3 gene was analysed by allele-specific matrix-assisted laser desorption ionization time-of-flight. Expression of NOS3 mRNA was tested in 72 patients of known genotype for NOS3 894 G>T. The clinical characteristics of these patients were obtained from medical records. Survival analysis showed that patients with AML (GG genotype) had a longer overall survival (OS; P = 0.006). After adjusting for age, gender, leucocyte count, haemoglobin level, platelet level, French, American and Britain (FAB) classification, lactate dehydrogenase levels, Eastern Cooperative Oncology Group Performance Status, nucleophosmin gene and fms-related tyrosine kinase 3 gene, multivariate survival analysis showed that the NOS3 894 G>T polymorphism appeared to be a predicting factor for OS (P = 0.014; hazard ratio = 1.856). However, no significant associations between the NOS3 894 G>T polymorphism and relapse-free survival and relapse in patients with AML were observed. Gene expression levels were significantly higher in patients with the GG genotype than in patients with the GT and TT genotypes (P = 0.033). The findings suggest that the NOS3 894 G>T variant may be a biomarker for the prediction of OS in Chinese patients with AML.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Benxi, China; Hunan Key Laboratory of Pharmacogenetics, Changsha, China; Department of Hematology, Benxi Central Hospital of China Medical University, Benxi, China.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Xu
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Qu
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Xu
authors.forename: Zhuo-Gang
authors.initials: ZG
authors.lastname: Liu
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.forename: Ming
authors.initials: M
authors.lastname: Zhai
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: acute myeloid leukaemia; chemotherapy; nitric oxide synthase 3; single nucleotide polymorphism