title: A TET2 rs3733609 C/T genotype is associated with predisposition to the myeloproliferative neoplasms harboring JAK2(V617F) and confers a proliferative potential on erythroid lineages.
abstract: Common germline single-nucleotide polymorphisms (SNPs) at JAK2 locus have been associated with Myeloproliferative neoplasms (MPN). And, the germline sequence variant rs2736100 C in TERT is related to risk of MPN, suggesting a complex association between SNPs and the pathogenesis of MPN. Our previous study (unpublished data) showed that there was a high frequency distribution in rs3733609 C/T genotype at Ten-Eleven Translocation 2 (TET2) locus in one Chinese familial primary myelofibrosis. In the present study, we evaluate the role and clinical significance of rs3733609 C/T genotype in JAK2V617F-positive sporadic MPN (n = 181). TET2 rs3733609 C/T genotype had a higher incidence (13.81%; 25/181) in JAK2V617F-positive sporadic MPN patients than that in normal controls (n = 236) (6.35%; 15/236), which was predisposing to MPN (odds ratio(OR) = 2.361; P = 0.01). MPN patients with rs3733609 C/T genotype had increased leukocyte and platelets counts, elevated hemoglobin concentration in comparison with T/T genotype. Thrombotic events were more common in MPN patients with rs3733609 C/T than those with T/T genotype (P < 0.01). We confirmed that rs3733609 C/T genotype downregulated TET2 mRNA transcription, and the mechanism may be involved in a disruption of the interaction between CCAAT/enhancer binding protein alpha (C/EBPA) and TET2 rs3733609 C/T locus.TET2 rs3733609 C/T genotype stimulated the erythroid hematopoiesis in MPN patients. Altogether, we found a novel hereditary susceptible factor-TET2 rs3733609 C/T variant for the development of MPN, suggesting the variant may be partially responsible for the pathogenesis and accumulation of MPN.
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Xiao-hui
authors: XH
authors: Shen
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Nan-nan
authors: NN
authors: Sun
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Ya-fei
authors: YF
authors: Yin
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Su-fang
authors: SF
authors: Liu
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Xiao-liu
authors: XL
authors: Liu
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Hong-ling
authors: HL
authors: Peng
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Chong-wen
authors: CW
authors: Dai
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Yun-xiao
authors: YX
authors: Xu
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Ming-yang
authors: MY
authors: Deng
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Yun-ya
authors: YY
authors: Luo
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Wen-li
authors: WL
authors: Zheng
authors: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors: Guang-sen
authors: GS
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008875:Middle Aged; D011087:Polycythemia Vera / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics*; D055815:Young Adult
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: TET2; clinical significance; mechanisms; myeloproliferative neoplasms; rs3733609