CCR2基因rs1799864多态性与儿童噬血性淋巴组织细胞增生症的关联研究

欧丹艳; 罗建明; 唐利娟

doi:10.7499/j.issn.1008-8830.2015.02.011

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中国当代儿科杂志 ›› 2015, Vol. 17 ›› Issue (2) : 164-167. DOI: 10.7499/j.issn.1008-8830.2015.02.011

论著·临床研究

CCR2基因rs1799864多态性与儿童噬血性淋巴组织细胞增生症的关联研究

欧丹艳, 罗建明, 唐利娟

作者信息 +

Association of CCR2 gene rs1799864 polymorphism with hemophagocytic lymphohistiocytosis in children

OU Dan-Yan, LUO Jian-Ming, TANG Li-Juan

Author information +

文章历史 +

摘要

目的探讨CCR2基因单核苷酸多态性(SNP)位点V64I(rs1799864)与儿童噬血性淋巴组织细胞增生症(HLH)发病的关联性.方法收集2007年1月至2013年12月确诊为HLH的86例患儿的临床资料,采用SNaPshot基因分型技术对HLH患儿和128例健康对照进行CCR2基因rs1799864位点分型,比较两组该SNP位点基因型和等位基因频率的差异;以及HLH患儿不同临床特征与rs1799864位点基因型分布的关系.结果与对照组相比,HLH组rs1799864位点的基因型和等位基因频率差异均无统计学意义(均P>0.05);就发病年龄是否<1岁、治疗后1 d体温是否恢复正常及治疗后2~3周血小板是否恢复正常等不同临床特征的HLH患儿基因型分布进行比较后发现差异均具有统计学意义(均P<0.05).结论 CCR2基因 rs1799864位点多态性与儿童HLH的发病无关,但其基因型不同可能与HLH患儿的临床表现及预后有关.

Abstract

Objective To investigate the association between rs1799864 single nucleotide polymorphism (SNP) of the C-C chemokine receptor 2 (CCR2) gene and susceptibility of hemophagocytic lymphohistiocytosis (HLH) in children. Methods The clinical and laboratory data of 86 children diagnosed with HLH between January 2007 and December 2013 were retrospectively reviewed. The CCR2 gene rs1799864 was genotyped by SNaPshot technique in 86 HLH children and 128 healthy controls. The genotypic and allelic frequencies in the two groups were comparatively analyzed. Results No significant difference either in genotypic or allelic frequencies of rs1799864 polymorphism of the CCR2 gene was observed between HLH patients and controls (P>0.05), but there were significant differences in the age of onset and the periods of temperature and platelet returning to normal after treatment (P<0.05). Conclusions There is no association between CCR2 gene rs1799864 polymorphism and the risk for HLH in children. However, the genotypic differences of this polymorphism might be associated with clinical characteristics and prognosis of HLH.

导出引用

欧丹艳, 罗建明, 唐利娟. CCR2基因rs1799864多态性与儿童噬血性淋巴组织细胞增生症的关联研究[J]. 中国当代儿科杂志. 2015, 17(2): 164-167 https://doi.org/10.7499/j.issn.1008-8830.2015.02.011

OU Dan-Yan, LUO Jian-Ming, TANG Li-Juan. Association of CCR2 gene rs1799864 polymorphism with hemophagocytic lymphohistiocytosis in children[J]. Chinese Journal of Contemporary Pediatrics. 2015, 17(2): 164-167 https://doi.org/10.7499/j.issn.1008-8830.2015.02.011

参考文献

[1] Risma K, Jordan MB. Hemophagocytic lymphohistiocytosis: updates and evolving concepts[J]. Curr Opin Pediatr, 2012, 24(1): 9-15.
[2] Henter JI, Horne AC, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis[J]. Pediatr Blood Cancer, 2007, 48(2): 124-131.
[3] Jordan MB, Hildeman D, Kappler J, et a1. An animal model of hemophagoeytic lymphohistiocytosis(HLH): CD8⁺ T cells and interferon gamma are essential for the disorder[J]. Blood, 2004, 104(3): 735-743.
[4] Sumegi J, Barnes MG, Nestheide SV, et al. Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis[J]. Blood, 2011, 117(15): e151-e160.
[5] 欧丹艳, 袁媛, 罗建明. 儿童噬血细胞性淋巴组织细胞增生症发病机制的生物信息学研究[J]. 医学研究生学报, 2014, 27(4): 382-386.
[6] Sezgin I, Koksal B, Bagci G, et al. CCR2 polymorphism in chronic renal failure patients requiring long-term hemodialysis[J]. Intern Med, 2011, 50(21): 2457-2461.
[7] Lin HL, Ueng KC, Hsieh YS, et al. Impact of MCP-1 and CCR-2 gene polymorphisms on coronary artery disease susceptibility[J]. Mol Biol Rep, 2012, 39(9): 9023-9030.
[8] Schürks M, Kurth T, Buring JE, et al. A candidate gene association study of 77 polymorphisms in migraine[J]. J Pain, 2009, 10(7): 759-766.
[9] 中华医学会儿科学分会血液学组. 噬血细胞性淋巴组织细胞增生症诊疗建议[J]. 中华儿科杂志, 2012, 50(11): 821-825.
[10] Clark MR, Massenburg D, Zhang M, et al. Molecular mechanisms of B cell antigen receptor traffificking[J]. Ann N Y Acad Sci, 2003, 987: 26-37.
[11] Rittig K, Peter A, Baltz KM, et al. The CCR2 promoter polymorphism T-960A, but not the serum MCP-1 level, is associated with endothelial function in prediabetic individuals[J]. Atherosclerosis, 2008, 198(2): 338-346.
[12] Cha SH, Lee JK, Lee JY, et al. Association of CCR2 polymorphisms with the number of closed coronary artery vessels in coronary artery disease[J]. Clin Chim Acta, 2007, 382(1-2): 129-133.
[13] Soto-Sánchez J, Santos-Juanes J, Coto-Segura P, et al. Genetic variation at the CCR5/CCR2 gene cluster and risk of psoriasis and psoriatic arthritis[J]. Cytokine, 2010, 50(2): 114-116.
[14] Kim HS, Kim DS, Lee EY, et al. CCR2-64Iand CCR5Delta32 polymorphisms in Korean patients with myasthenia gravis[J]. J Clin Neurol, 2007, 3(3): 133-138.
[15] Huerta C, Alvarez V, Mata IF, et al. Chemokines (RANTES and MCP-1) and chemokine-receptors (CCR2 and CCR5) gene polymorphisms in Alzheimer's and Parkinson's disease[J]. Neurosci Lett, 2004, 370(2-3): 151-154.
[16] Jordan MB, Allen CE, Weitzman S, et al. How I treat hemophagocytic lymphohistiocytosis[J]. Blood, 2011, 118(15): 4041-4052.
[17] Trottestam H, Berglöf E, Horne A, et al. Risk factors for early death in children with haemophagocytic lymphohistiocytosis[J]. Acta Paediatr, 2012, 101(3): 313-318.
[18] 陆文娴, 罗建明. 儿童噬血细胞性淋巴组织细胞增生症的预后因素分析[J]. 中国当代儿科杂志, 2012, 14(8): 593-597.
[19] Onufer JJ, Horuk R. Chemokines, chemokine receptors and small-molecule antagonists: recent developments[J]. Trends Pharmacol Sci, 2002, 23(10): 459-467.
[20] Abbadie C, Lindia JA, Cumiskey AM, et al. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2[J]. Proc Natl Acad Sci U S A, 2003, 100(13): 7947-7952.