免疫基因多态性与衰老和增龄相关疾病关系

doi:10.3724/SP.J.1005.2013.00813

遗传 ›› 2013, Vol. 35 ›› Issue (7): 813-822.doi: 10.3724/SP.J.1005.2013.00813

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免疫基因多态性与衰老和增龄相关疾病关系

阮清伟¹, 俞卓伟^1,2, 保志军¹, 马永兴²

1. 复旦大学上海医学院附属华东医院中心实验室, 上海 200040 2. 复旦大学上海医学院, 上海市老年医学研究所, 衰老、抗衰老和认知功能研究室, 上海 200040

收稿日期:2013-01-22 修回日期:2013-03-26 出版日期:2013-07-20 发布日期:2013-07-25
通讯作者: 俞卓伟 E-mail:fdhuadong@163.com
基金资助:
复旦大学985平台建设基金项目(编号：985III-YFX0603)和上海市重点学科建设基金项目(编号：05III015)资助

The relationship between the polymorphism of immunity genes and both aging and age-related diseases

RUAN Qing-Wei¹, YU Zhuo-Wei^1,2, BAO Zhi-Jun¹, MA Yong-Xing²

1. Central Laboratory, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China 2. Department of Aging, Antiaging and Cognitive Function, Shanghai Institute of Geriatrics and Gerontology, Shanghai Medical College, Fudan University, Shanghai 200040, China

Received:2013-01-22 Revised:2013-03-26 Online:2013-07-20 Published:2013-07-25

摘要/Abstract

摘要： 衰老是进行性的、多细胞普遍存在的、不可逆的功能减退状态。免疫衰老主要表现为造血干细胞再生和淋巴系分化能力下降、机体对感染和疫苗的反应减弱、对炎症反应的放大和自身的免疫反应增加, 与衰老和增龄相关疾病密切相关。免疫基因变异, 影响机体免疫反应, 可加速或延缓衰老和增龄相关疾病。获得性免疫基因, 如对自身免疫性疾病起保护性作用的HLA II 抗原基因DRB1*11和DRB*16相关的单倍型在长寿老人频率增加。抗炎因子IL-10-1082G等位基因频率和TGFβ1单倍型cnd10T/C、cnd25G/G、-988C/C、-800G/A频率的下降, 促炎因子TNFα低表达相关的扩展的TNF-A基因型-1031C/C、-863C/A、-857C/C、IL-6-174 CC基因型, 和IFN-γ+874 T等位基因频率减少与免疫炎症反应易感性, 衰老相关疾病的发病率和死亡率正相关。固有免疫基因, 如高频表达抗炎的+896 G KIR4等位基因、CCR5Δ32突变、-765 C Cox-2等位基因、-1708 G和21 C 5-Lox等位基因多见于长寿老人。KIR 单倍型 KIR2DS5、A1B10减少, MBL2表达缺乏的单倍型LYPB、LYQC 和HYPD增加的老年人常伴有较高血清CMV抗体滴度。高频出现的CRP ATG单倍型和CFH 402 His 等位基因预示老年人高死亡率风险。文章对固有和获得性免疫基因多态性、单倍体与衰老及衰老相关疾病关系进展进行综述。加强分析扩展的单倍型、表观遗传学和造血干细胞衰老的遗传学研究将有助于更好地理解衰老和长寿的免疫遗传学基础。

关键词: 免疫基因多态性, 单倍型, 衰老, 增龄相关疾病

Abstract: Aging is acommon, progressive and irreversible state of multi-cell dysfunction. Immune aging mainly includes the declines of regenerative capacity and lymphoid lineage differentiation potential, the hyporesponsive to infection and vaccination, the hyperresponsive in the context of inflammatory pathology, and the increased risk of autoimmunity. The dysfunction of aged immune system accelerates the occurrence of aging and age-related diseases. The mutation of immunity genes that affect immune responses accelerates or slows aging process and age-related diseases. The frequencies of acquired immunity genes, such as immune protective HLA II DRB1*11 and DRB*16-associated haplotype, are increased in the longevity populations. The increased susceptibility of immune inflammatory response, morbidity and mortality in the elderly is often associated with decreased frequencies of anti-inflammatory factor IL-10 -1082G allele, TNF-β1 haplotype cnd10T/C, cnd25G/G, –988C/C, –800G/A, low proinflammatory fator TNFa level related extended TNF-A genotype –1031C/C, –863C/A, –857C/C, IL-6-174 CC and IFN-γ+874 T allele as well. The innate immunity genes, such as highly expressed anti-inflammatory +896 G KIR4 allele, CCR5Δ32 variant, –765 C Cox-2 allele, –1708 G and 21 C 5-Lox alleles are detected in centenarians. In age-related diseases, a higher CMV-specific IgG antibody level in elderly individuals is associated with a decreased frequency of KIR haplotypes KIR2DS5 and A1B10 and an increased frequency of MBL2 haplotypes LYPB, LYQC and HYPD that result in the absence of MBL2 protein. The increased frequencies of CRP ATG haplotypes and CFH 402 His allele indicate high mortality in the elderly. In the present study, we review the advances in the polymorphism and haplotype of innate and adoptive immunity genes, and their association with both aging and age-related diseases. To strengthen the analysis of extended haplotypes, epigenetic studies of immunity genes and genetic study of hematopoietic stem cell senescence will be helpful to understand the accurate basis of aging-related immune genetics better.

Key words: polymorphism of immunity genes, haplotype, aging, age-related diseases

阮清伟俞卓伟保志军马永兴. 免疫基因多态性与衰老和增龄相关疾病关系[J]. 遗传, 2013, 35(7): 813-822.

RUAN Qing-Wei YU Zhuo-Wei BAO Zhi-Jun MA Yong-Xing. The relationship between the polymorphism of immunity genes and both aging and age-related diseases[J]. HEREDITAS, 2013, 35(7): 813-822.

参考文献

[1] De la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging: The involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des, 2009, 15(26): 3003-3026.
[2] Sebastiani1 P, Solovieff1 N, DeWan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Hoh J, Perls TT. Genetic signatures of exceptional lon-gevity in humans. PloS One, 2012, 7(1): e29848.
[3] Ruan QW, Liu F, Gao ZJ, Kong DQ, Hu XN, Shi DM, Bao ZJ, Yu ZW. The anti-inflammaging and hepatoprotective effects of huperzine A in D-galactose-treated rat. Mech Ageing Dev, 2013; 134(3-4): 89-97.
[4] Naumova E, Ivannova M, Pawelec G. Immunogenetics of ageing. Int J Immunogenet, 2011, 38(5): 373-381.
[5] 孔放, 张根发, 吕泽平, 孙亮, 郑陈光, 梁积英, 朱小泉, 杨泽. 人类长寿相关基因研究进展. 遗传, 2006, 28(7): 874-879.
[6] 俞卓伟, 保志军, 阮清伟, 马永兴. 氧化应激-炎症-衰老及其与ApoE基因相关性研究进展. 生理学报, 2013, 65(3): 338-346.
[7] Naumova E, Ivanova M, Pawelec G, Constantinescu I, Bogunia-Kubik K, Lange A, Oguz F, Ozdilli K, Franceschi C, Caruso C, Mishra M, Middleton D. 16th IHIW: Immunogenetics of aging. Int J Immunogenet, 2013, 40(1): 77-81.
[8] Fulop T, Larbi A, Kotb R, de Angelis F, Pawelec G. Aging, immunity, and cancer. Discov Med, 2011, 11(61): 537-550.
[9] Balistreri CR, Candore G, Accardi G, Bova M, Buffa S, Bulati M, Forte GI, Listì F, Martorana A, Palmeri M, Pel-licanò M, Vaccarino L, Scola L, Lio D, Colonna-Romano G. Genetics of longevity. data from the studies on Sicilian centenarians. Immun Ageing, 2012, 9(1): 8.
[10] Hurme M, Kivimaki M, Pertovaara M, Lehtimäki T, Karhunen PJ, Jylhä M, Hervonen A, Eklund C. CRP gene is involved in the regulation of human longevity: a follow-up study in finnish nonagenarians. Mech Ageing Dev, 2007, 128(10): 574-576.
[11] Laine M, Jarva H, Seitsonen S, Haapasalo K, Lehtinen MJ, Lindeman N, Anderson DH, Johnson PT, Jarvela I, Jokiranta TS, Hageman GS, Immonen I, Meri S. Y402H polymorphism of complement factor H affects binding af-finity to C-reactive protein. J Immunol, 2007, 178(6): 3831-3836.
[12] Jylhävä J, Eklund C, Jylhä M, Hervonen A, Lehtimäki T, Karhunen P, Hurme M. Complement factor H 402His variant confers an increased mortality risk in finnish nonagenarians: the vitality 90+ study. Exp Gerontol, 2009, 44(4): 297-299.
[13] Naumova E, Pawelec G, Ivanova M, Constantinescu I, Bogunia-Kubik K, Lange A, Qguz F, Carin M. 14th International HLA and Immunogenetics Workshop: report on the immunogenetics of aging. Tissue Antigens, 2007, 69(Suppl 1): 304-310.
[14] Becerril EV, Fern?ndez RG, Torres LP, Lacomba MS, Galera JMG. HLA B27 as predisposition factor to suffer age related macular degeneration. Cell Mol Immunol, 2009, 6(4): 303-307.
[15] Listì F, Caruso C, Colonna-Romano G, Lio D, Nuzzo D, Candore G. HLA and KIR frequencies in Sicilian Cente-narians. Rejuvenation Res, 2010, 13(2-3): 314-318.
[16] Iannitti T, Palmieri B. Inflammation and genetics: an in-sight in the centenarian model. Hum Biol, 2011, 83(4): 531-559.
[17] Jylhävä J, Hurme M. Gene variants as determinants of Longevity: focus on the inflammatory factors. Pflugers Arch, 2010, 459(2): 239-246.
[18] Naumova E, Ivanova M, Pawelec G, Constantinescu I, Bogunia-Kubik K, Lange A, Qguz F, Carin M, Franceschi C, Caruso C, Middleton D. ‘Immunogenetics of Aging’: report on the activities of the 15th international HLA and immunogenetics working group and 15th international HLA and immunogenetics workshop. Tissue Antigens, 2011, 77(3): 187-192.
[19] Scola L, Licastro F, Chiappelli M, Franceschi C, Grimaldi LM, Crivello A, Colonna-Romano G, Candore G, Lio D, Caruso C. Allele frequencies of +874T → A single nu-cleotide polymorphism at the first intron of IFN-gamma gene in Alzheimer's disease patients. Aging Clin Exp Res, 2003, 15(4): 292-295.
[20] Vaccarino L, Vitale S, Caruso M, Palmeri M, Scola L, Bova M, Caruso C, Massenti MF, Vitale F, Novo S, Lio D, Forte GI. Myocardial infarction marker levels are influenced by prothrombin and tumor necrosis factor-α gene polymorphisms in young patients. Cytokine, 2013, 61(1): 218-222.
[21] Khabour OF, Barnawi JM. Association of longevity with IL-10-1082 G⁄A and TNF-α-308 G⁄A polymorphisms. Int J Immunogenet, 2010, 37(4): 293-298.
[22] Balistreri CR, Colonna-Romano G, Lio D, Candore G, Caruso C. TLR4 polymorphisms and ageing: implications for the pathophysiology of age-related diseases. J Clin Immunol, 2009, 29(4): 406-415.
[23] Listì F, Caruso M, Incalcaterra E, Hoffmann E, Caimi G, Balistreri CR, Vasto S, Scafidi V, Caruso C, Candore G. Pro-inflammatory gene variants in myocardial infarction and longevity: implications for pharmacogenomics. Curr Pharm Des, 2008, 14(26): 2678-2685.
[24] Balistreri CR, Grimaldi MP, Chiappelli M, Licastro F, Castiglia L, Listì F, Vasto S, Lio D, Caruso C, Candore G. Association between the polymorphisms of TLR4 and CD14 genes and Alzheimer's disease. Curr Pharm Des, 2008, 14(26): 2672-2677.
[25] Balistreri CR, Caruso C, Carruba G, Miceli V, Campisi I, Listì F, Lio D, Colonna-Romano G, Candore G. A pilot study on prostate cancer risk and pro-inflammatory geno-types: pathophysiology and therapeutic implications. Curr Pharm Des, 2010, 16(6): 718-724.
[26] Aïd S, Bosetti F. Targeting cyclooxygenases-1 and -2 in neuroinflammation: therapeutic implications. Biochimie, 2011, 93(1): 46-51.
[27] Dwyer JH, Allayee H, Dwyer KM, Fan J, Wu HY, Mar R, Lusis AJ, Mehrabian M. Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and athero-sclerosis. N Engl J Med, 2004, 350(1): 29-37.
[28] Cipollone F, Fazia ML. COX-2 and atherosclerosis. J Cardiovasc Pharmacol, 2006, 47(Suppl. 1): S26-S36.
[29] Papafili A, Hill MR, Brull DJ, McAnulty RJ, Marshall RP, Humphries SE, Laurent GJ. Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response. Arterioscler Thromb Vasc Biol, 2002, 22(10): 1631-1636.
[30] Balistreri CR, Caruso C, Grimaldi MP, Listì F, Vasto S, Orlando V, Campagna AM, Lio D, Candore G. CCR5 receptor: biologic and genetic implications in age-related diseases. Ann N Y Acad Sci, 2007, 1100(1): 162-172.
[31] Balistreri CR, Candore G, Caruso M, Incalcaterra E, Franceschi C, Caruso C. Role of polymorphisms of CC-chemokine receptor-5 gene in acute myocardial infarction and biological implications for longevity. Haematologica, 2008, 93(4): 637-638.
[32] Laplana M, Fibla J. Distribution of functional polymor-phic variants of inflammation-related genes RANTES and CCR5 in long-lived individuals. Cytokine, 2012, 58(1): 10-13.
[33] Maxwell LD, Ross OA, Curran MD, Rea IM, Middleton D. Investigation of KIR diversity in immunosenecence and longevity within the Irish population. Exp Gerontol, 2004, 39(8): 1223-1232.
[34] Li G, Yu MC, Weyand CM, Goronzy JJ. Epigenetic regu-lation of killer immunoglobulin-like receptor expression in T cells. Blood, 2009, 114(16): 3422-3430.
[35] Liu Y, Chen YX, Richardson B. Decreased DNA methyl-transferase levels contribute to abnormal gene expression in “senescent” CD4+CD28-T cells. Clin Immunol, 2009, 132(2): 257-265.
[36] Jobim M, Chagastelles P, Salim PH, Portela P, Wilson TJ, Curti AG, Jobim MR, João DA, Nardi NB, Tschiedel B, Jobim LF, Roesler R, Schwartsmann G. Association of killer cell immunoglobulin-like receptors and human leu-kocyte antigen-C genotypes in South Brazilian with type 1 diabetes. Hum Immunol, 2010, 71(8): 799-803.
[37] Zaia JA, Sun JY, Gallez-Hawkins GM, Thao L, Oki A, Lacey SF, Dagis A, Palmer J, Diamond DJ, Forman SJ, Senitzer D. The effect of single and combined activating killer immunoglobulin-like receptor genotypes on cy-tomegalovirus infection and immunity after hematopoietic cell transplantation. Biol Blood Marrow Transplant, 2009, 15(3): 315-325.

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免疫基因多态性与衰老和增龄相关疾病关系

The relationship between the polymorphism of immunity genes and both aging and age-related diseases

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