摘要
目的探讨IL-10基因启动子区域- 1082、- 819和- 592位点单核苷酸多态性与脑梗死的关系。
方法用扩增受阻突变系统-聚合酶链反应(ARMS-PCR)技术,对181例脑梗死患者(脑梗死组)和115名健康者(对照组)的IL-10基因启动子区域- 1082A/G、- 819C/T和- 592A/C位点核甘酸多态性进行分析。
结果脑梗死组IL-10-1082A/G基因型的分布频率与对照组比较,差异有统计学意义(χ~2=6.643 P=0.010);A等位基因频率为92.3%,对照组为86.1%,两组比较差异有统计学意义(P=0.015);IL-10-819C/T和IL-10-592C/A的基因型分布频率及等位基因频率与对照组比较差异无统计学意义(P>0.05)。
结论IL-10-1082A/G基因多态性与脑梗死的发病有关,其中A等位基因频率增高与脑梗死发病有关。
Object To investigate whether three diallelic polymorphisms at the position - 1082,- 819 and - 592 in the promoter region of the IL-10 gene were associated with cerebral infarction(CI).
Methods The IL-10 gene - 1082, - 819 and - 592 position polymorphisms were genotyped by amplification refractory mutation systems-polymerase chain reaction (ARMS-PCR) methods in 181 patients with cerebral infarction(CI group) and 115 healthy subjects (control group). Results There was statistical significance in the distribution frequency of IL-10-1082G/A allele in the CI group as compared with the control group (χ~2 = 6.643 ,P=0.010).The IL-10-1082 A allele frequency was 92.3%,and the control group was 86.1%;there was statistical significance between the two groups(P=0.015).There were no statistical significance in genotype distribution frequency of IL-10-592C/A and -819C/T and allele frequency as compared with the control group (P>0.05).
Conclusion IL-10-1082G/A gene polymorphisms have been involved in CI,in which the increased A allele frequency is associated with the occurrence of CI.
引文
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[1] Fiorentino DF,Bond MW ,Mosmann TR.Two types of mouse T helper cell:Th2 clones secrete a factor that inhibits cytokine production by Thl clones.J Exp Med,1989,170:2081-2095
[2]O’Garra A, Vieira P. T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol 2007;7:425–428.
[3] Fillatreau S, Gray D, Anderton SM. Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol 2008;8:391–397.
[4] Ryan JJ, et al. Mast cell homeostasis: a fundamental aspect of allergic disease. Crit Rev Immunol 2007;27:15–32.
[5]Moore KW, de Waal MR, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001;19:683–765.
[6] Williams LM, Ricchetti G, Sarma U, Smallie T,Foxwell BM. Interleukin-10 suppression of myeloid cell activation-a continuing puzzle.Immunology 2004;113:281–292.
[7] Kim JM,Brannan CI,Copeland NG,et al.Structure of the mouse IL-10 gene and chromosomal location of the mouse and human genes.J Immunol,1992;148:3618-3623
[8]Keystone E,Wherry J,Crint P,et al.IL-10 as a therapeutic strategy in the treatment of rheumatoid arthritis. Rheu Dis Clin Noth Am,1998,24:629-639.
[9]Cai G, Kastelein RA, Hunter CA. IL-10 enhances NK cell proliferation, cytotoxicity and production of IFN-gamma when combined with IL-18. Eur J Immunol 1999;29:2658-2665.
[10] Santin AD, et al. Interleukin-10 increases Th1 cytokine production and cytotoxic potential in human papillomavirus-specific CD8(+) cytotoxic T lymphocytes. J Virol 2000;74:4729-4737.
[11]Rowbottom AW, Lepper MA, Garland RJ, Cox CV, Corley EG. Interleukin-10-induced CD8 cell proliferation. Immunology 1999;98:80–89.
[12] Groux H, Bigler M, de Vries JE, Roncarolo MG. Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells. J Immunol 1998;160:3188-3193.
[13]Libby P, Hansson GK. Involvement of the immune system in human atherosclerosis:current knowledge and unanswered questions [J]. Lab Invest, 1991, 64: 5-15.
[14]Mallat Z, Heymes C,Ohan J ,et al. Expression of interleukin-10 in advanced human atherosclerosis plaques: relation to inducible nitric oxide synthase expression and cell death [J]. Arterioscler Thromb Vasc Biol,1999,19(3):611-616.
[15] Mallat Z, Besnard S, Duriez M, et al.Protective role of interleukin-10 in atherosclerosis[J]. Circ Res. 1999 85(8):e17-24.
[16]David P, Hajjar,Andrew C,Nicholson. Atherosclerosis-A understanding of the cellular and molecular basis of the disease promise new approaches for its treatment in the near future[J]. American Scientiet,1995,83: 460-467.
[17]Dinarello CA. Modalities for reducing interleukin-1 activity in disease[J]. Immunol Today,1993,14(6):260-264.
[18]Kucharzik T,Lugering N,Pauels HG, et al. IL-4, IL-10 and IL-13 downregulate monocyte-chemoattracting protein-1 (MCP-1)production in activated intestinal cells[J]. Clin Exp Immunol, 1998,111:152-157
[19]Gosling J,Slaymaker S, Gu L ,et al. MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipop rotein B [J]. J Clin Invest,1999,103:773-778.
[20]Lindmark E, Tenno T, Chen J, et al.IL-10 inhibits LPS-induced human monocyte tissue factor expression in whole blood[J].Br J Haematol. 1998 102(2):597-604.
[21]Westendorp RG,Langermans JA,Huizinga TW,et a1.Genetic influence on cytokine production and fatal meningococcal disease.Lancet,1997,349:170-173.
[22]Turner DM,Williams DM,Sankaran D,et a1.An investigation of polymorphism in the interleukin-10 gene promoter.Eur J Immunogenet,1997,24(1):1-8.
[23] D'Alfonso S, Rampi M, Rolando V,et a1.New polymorphisms in the IL- 10 promoter region.Genes Immune.2000,1(3):231-233.
[24]Perrey C, Turner SJ, Pravica V, et al. ARMS-PCR methodologies to determine IL-10, TNF-α, TNF-βand TGF-β1 gene polymorphisms.Transplant Immunol, 1999, 7: 127-128.
[25]Hoffmann SC,Stanley EM ,Cox ED, et al.Ethnicity greatly influences cytokine gene polymorphism distribution.Am J Transplant,2002,2:560 -567.
[26]Mok CC,Lanchbury JS,Chan DW ,et a1.Interleukin-10 promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus.Arthritis Rheum ,1998,41:1090-1095.
[27]Hu RC,Xu YJ,Zhang ZX,et a1.Polymorphism of interleukin-10 gene promoter and its association with susceptibility to chronic obstructive pulmonary disease in Chinese Han people.Chin J Med Genet,2003,20:504-507.
[28]Hofmann SC,Stanley EM,Darrin Cox E,et a1.Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28 stimulated peripheral blood Lymphocytes.Transplantation,2001,72:1444-1450.
[29]Gonsalkorale WM,Perrey C,Pravica V,et a1.Interleukin-10 genotypes in irritable bowel syndrome:evidence for an inflammatory component.Gut,2003,52:91-93.
[30]Lazarus M,Hajeer AH,Turner D,et a1.Genetic variation in the interleukin-10 gene promoter and systemic lupus erythematosus.J Rheumatol,1997,24:2273-2275.
[31]Seayel-Caminaga RM ,Trevilatto PC,Souza AP,et a1.Interleukin-10 gene promoter polymorphisms are associated with chronic periodontitis.J Clin Periodontol,2004,31:443-448.
[32]Knapp S,Hennig BJ,Frodsham AJ,et a1.Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection.Immunogenetics,2003,55:362-369.
[33]Mangia A,Santoro R,Piattelli M ,et al.IL-10 haplotypes as possible predictors of spontaneous clearance of HCV infection.Cytokine,2004,25:103-109.
[34]Catto AJ,Carter AM,Stickland M,et al . Plasminogen activator inhibitor-1(PAI-1)4G/5C promoter polymorphism and levels in subjects with cerebrovascular disease.Thromb Haemost l997:77(4):730-734.
[35]刘楠,陈荣华,郑安,等. IL-lO对大鼠脑缺血损伤保护作用的研究[J].中国药学杂志,2005,40(13):988-990.
[36]Grilli M,Barbieri I,Basudev H,et al.Interleukin-10 modulates neuronal threshold of vulnerability to ischaemic damage[J] . Eur J Neurosci,2000,12(7):226
[37]Homell TM,Beresford GW,Bushey A,et al.Regulation of the class II MHC pathway in primary human monocytes by granulocyte-marophage colony-stimulating factor[J].J Immunol,2003,171(5):2374.
[38]Hopkins SJ,Rothwell NJ,Cytokines and the nervous system:expression and recognition,Trends Neurosci,1995,18:83-88.
[39]Pahan K,Khan MQ,Singh IJ.Interleukin-10 and interleukin-13 inhibit proinflammatory cytokine-induced ceramide production through theactivation of phosphatidylinositol 3-Kinase[J].J Neurochem,2000,75(2):576.
[40]Perini F , Mona M , Alecci M , et al.temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients[J].Neurol Sci,2001,22(4):289.
[41]Li HL,Kostulas N,Huang YM,et a1.IL-17 and IFN-gamma mRNA expression is increased in the brain and systemically after permanent middle cerebral artery occlusion in the rat[J].Neuroimmunol,2001,116:5-14.
[42] van Exel E,Gussekloo J,de Craen AJ,et a1.Inflammation and stroke:the Leiden 85-Plus Study[J].Stroke,2002, 33:1135-1138.
[43] Grilli M,Barbieri I,Basudev H,et a1.Interleukin-10 modulates neuronal threshold of vulnerability to ischaemic damage[J].Eur Neurosci,2000,12:2265-2272.
[44]Koch W,Kastrati A,Bottiger C,et a1.Interleukin-10 and tumor necrosis factor gene polymorphisms and risk of coronary artery disease and myocardial infarction[J].Atherosclerosis,2001,159:137-144.
