An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males
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作者:
Do, Thuy N.
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HUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USAHUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USA
Do, Thuy N.
[1
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Ucisik-Akkaya, Esma
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HUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USAHUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USA
Ucisik-Akkaya, Esma
[1
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Davis, Charronne F.
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HUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USAHUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USA
Davis, Charronne F.
[1
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Morrison, Brittany A.
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HUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USAHUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USA
Morrison, Brittany A.
[1
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Dorak, M. Tevfik
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HUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USAHUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USA
Dorak, M. Tevfik
[1
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机构:
[1] HUMIGEN LLC, Inst Genet Immunol, Genom Immunoepidemiol Lab, Hamilton, NJ 08690 USA
来源:
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2010年
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1802卷
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02期
The interferon regulatory factor (IRF) family of DNA-binding proteins regulates expression of interferon-inducible genes with roles in the immune response and carcinogenesis. IRF4 is involved in the differentiation of B and T cells and is overexpressed in B-cell malignancies as a result of c-REL (NF-kappa B) hyperactivation. IRF4 polymorphisms are associated with susceptibility to chronic lymphoid leukemia (CLL) and non-Hodgkin lymphoma (NHL). We examined 13 IRF4 SNPs in 114 cases of childhood acute lymphoblastic leukemia (ALL) and 388 newborn controls from Wales (U.K.) using TaqMan assays. IRF4 intron 4 SNP rs12203592 showed a male-specific risk association (OR = 4.4. 95% CI = 1.5 to 12.6, P = 0.007). Functional consequences of the C>T substitution at this SNP were assessed by cell-based reporter assays using three different cell lines. We found a repressive effect of the rs12203592 wildtype allele C on IRF4 promoter activity (P<0.001) but no repression by the variant allele in any cell line tested. Thus, homozygosity for the rs12203592 variant allele would result in increased IRF4 expression. This increase would be compounded by high levels of NF-kappa B activity in males due to the absence of estrogen. IRF4 differs from other IRFs in its anti-interferon activity which interferes with immune surveillance. We propose that a detailed study of IRF4 can provide information on the mechanism of the sex effect and the role of immune surveillance in childhood ALL development. (C) 2009 Elsevier B.V. All rights reserved.
机构:
Jinan Univ, Dept Pediat, Clin Coll Med 1, Guangzhou Overseas Chinese Hosp, Guangzhou, Guangdong, Peoples R ChinaJinan Univ, Dept Pediat, Clin Coll Med 1, Guangzhou Overseas Chinese Hosp, Guangzhou, Guangdong, Peoples R China
Li, Yuhua
Wang, Huihui
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Shenzhen Childrens Hosp, Div Hematol & Oncol, 7019 Yi Tian Rd, Shenzhen 518038, Guangdong, Peoples R ChinaJinan Univ, Dept Pediat, Clin Coll Med 1, Guangzhou Overseas Chinese Hosp, Guangzhou, Guangdong, Peoples R China
Wang, Huihui
Chen, Xiaowen
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Shenzhen Childrens Hosp, Div Hematol & Oncol, 7019 Yi Tian Rd, Shenzhen 518038, Guangdong, Peoples R ChinaJinan Univ, Dept Pediat, Clin Coll Med 1, Guangzhou Overseas Chinese Hosp, Guangzhou, Guangdong, Peoples R China
Chen, Xiaowen
Mai, Huirong
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Shenzhen Childrens Hosp, Div Hematol & Oncol, 7019 Yi Tian Rd, Shenzhen 518038, Guangdong, Peoples R ChinaJinan Univ, Dept Pediat, Clin Coll Med 1, Guangzhou Overseas Chinese Hosp, Guangzhou, Guangdong, Peoples R China
Mai, Huirong
Li, Changgang
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Shenzhen Childrens Hosp, Div Hematol & Oncol, 7019 Yi Tian Rd, Shenzhen 518038, Guangdong, Peoples R ChinaJinan Univ, Dept Pediat, Clin Coll Med 1, Guangzhou Overseas Chinese Hosp, Guangzhou, Guangdong, Peoples R China
Li, Changgang
Wen, Feiqiu
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Shenzhen Childrens Hosp, Div Hematol & Oncol, 7019 Yi Tian Rd, Shenzhen 518038, Guangdong, Peoples R ChinaJinan Univ, Dept Pediat, Clin Coll Med 1, Guangzhou Overseas Chinese Hosp, Guangzhou, Guangdong, Peoples R China
机构:
Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Wang, Zijie
Zhang, Hengcheng
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Zhang, Hengcheng
Yang, Haiwei
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Yang, Haiwei
Zheng, Ming
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Zheng, Ming
Guo, Miao
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Nanjing Med Univ, Affiliated Hosp 1, Res Div Clin Pharmacol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Guo, Miao
Chen, Hao
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Chen, Hao
Sun, Li
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Sun, Li
Han, Zhijian
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Han, Zhijian
Tao, Jun
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Tao, Jun
Ju, Xiaobing
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Ju, Xiaobing
Tan, Ruoyun
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Tan, Ruoyun
Wei, Ji-Fu
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Nanjing Med Univ, Affiliated Hosp 1, Res Div Clin Pharmacol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
Wei, Ji-Fu
Gu, Min
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Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R ChinaNanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Peoples R China
机构:
Nanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
Nanjing Red Cross Blood Ctr, Nanjing 210003, Jiangsu, Peoples R ChinaNanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
Luo, Ying
Yu, Luting
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China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 210009, Jiangsu, Peoples R ChinaNanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
Yu, Luting
Yu, Tingting
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机构:
Nanjing Med Univ, Sch Basic Med Sci, Dept Dev Genet, Nanjing 210029, Jiangsu, Peoples R ChinaNanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
Yu, Tingting
Jiang, Feixia
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Nanjing Med Univ, Nanjing Hosp 1, Dept Lab Med, Nanjing 210006, Jiangsu, Peoples R ChinaNanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
Jiang, Feixia
Cai, Xubing
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Nanjing Red Cross Blood Ctr, Nanjing 210003, Jiangsu, Peoples R ChinaNanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
Cai, Xubing
Zhao, Yilun
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Nanjing Red Cross Blood Ctr, Nanjing 210003, Jiangsu, Peoples R ChinaNanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
Zhao, Yilun
Pan, Shiyang
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Nanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R ChinaNanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
Pan, Shiyang
Luo, Chen
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机构:
China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 210009, Jiangsu, Peoples R ChinaNanjing Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China