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芬兰百岁老人中人类长寿与白细胞介素-1簇、白细胞介素-6、白细胞介素-10和肿瘤坏死因子-α基因多态性之间不存在关联。

Lack of association between human longevity and polymorphisms of IL-1 cluster, IL-6, IL-10 and TNF-alpha genes in Finnish nonagenarians.

作者信息

Wang X Y, Hurme M, Jylhä M, Hervonen A

机构信息

Department of Gerontology, School of Public Health, University of Tampere, FIN-33014, Tampere, Finland.

出版信息

Mech Ageing Dev. 2001 Dec;123(1):29-38. doi: 10.1016/s0047-6374(01)00338-4.

DOI:10.1016/s0047-6374(01)00338-4
PMID:11640949
Abstract

There has been increasing interest in research on genetic basis of longevity. Aging is accompanied by immune deterioration and dysregulation of cytokines. Increased IL-6 concentration in vivo and enhanced IL-6, IL-1beta, and TNF-alpha production in vitro have been reported in healthy elderly people. Cytokine gene polymorphisms have been demonstrated to be associated with cytokine production both in vivo and in vitro, and with some diseases. Thus, gene polymorphisms of cytokine may play a role in longevity by modulating an individual's responses to life-threatening disorders. Cytokine gene polymorphisms at IL1A-889, IL1B+3953, IL1B-511, IL1RN VNTR, IL6-174, IL10-1082, and TNFA-308 were genotyped in 250 Finnish nonagenarians (52 men and 198 women) and in 400 healthy blood donors (18-60 years) as controls. No statistically significant differences were found in the genotype distributions, allelic frequencies and A2+ carrier status of IL-1alpha, IL-1beta, IL-1RA, IL-6, IL-10, and TNF-alpha genes between nonagenarians and younger controls within Finnish population, nor between male and female nonagenarians. No differences emerged between nonagenarians and younger controls by comparing different IL-1 gene cluster haplotypes. Thus, there is no evidence of an association of IL-1 complex, IL-6, IL-10, and TNF-alpha gene polymorphisms with longevity, alone or in combination.

摘要

人们对长寿的遗传基础研究兴趣日益浓厚。衰老伴随着免疫功能衰退和细胞因子失调。据报道,健康老年人体内白细胞介素-6(IL-6)浓度升高,体外IL-6、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的产生增强。细胞因子基因多态性已被证明与体内外细胞因子的产生以及某些疾病有关。因此,细胞因子基因多态性可能通过调节个体对危及生命疾病的反应而在长寿中发挥作用。对250名芬兰百岁老人(52名男性和198名女性)以及400名健康献血者(18至60岁)作为对照,对IL1A - 889、IL1B + 3953、IL1B - 511、IL1RN VNTR、IL6 - 174、IL10 - 1082和TNFA - 308处的细胞因子基因多态性进行基因分型。在芬兰人群中,百岁老人与年轻对照之间,以及男性和女性百岁老人之间,IL - 1α、IL - 1β、IL - 1RA、IL - 6、IL - 10和TNF - α基因的基因型分布、等位基因频率和A2 +携带者状态均未发现统计学上的显著差异。通过比较不同的IL - 1基因簇单倍型,百岁老人与年轻对照之间也未出现差异。因此,没有证据表明IL - 1复合体、IL - 6、IL - 10和TNF - α基因多态性单独或联合与长寿有关。

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