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.

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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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