Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly
Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly
复制标题
DOI：
10.1016/s0531-5565(03)00209-2
复制
发表时间：
2003-10-01
影响因子：
3.9
通讯作者：
De Benedictis, G
中科院分区：
文献类型：
--
作者：
Rose, G;Dato, S;De Benedictis, G
人类沉默调节蛋白3（SIRT3）基因编码一种假定的线粒体NAD依赖的去乙酰化酶（SIRT3），它属于进化上保守的沉默调节蛋白家族。在模式生物中的研究表明，SIR2基因控制寿命，然而关于SIRT3在人类长寿中可能的作用尚无相关数据。通过分析与SIRT3的G477T标记相关的基因型特异性生存函数，我们发现，在男性中，TT基因型增加了（p = 0.0272）老年人的生存率，而GT基因型则降低了（p = 0.0391）老年人的生存率。由于SIRT3位于一个染色体区域（11p15.5），该区域有四个可能与长寿相关的基因（HRAS1、胰岛素样生长因子2、胰岛素原和酪氨酸羟化酶），我们检测了G477T等位基因与上述基因的等位基因之间的连锁不平衡。在任何情况下，这种不平衡都不显著，因此表明SIRT3本身，或者一个与SIRT3紧密连锁的基因，可能在人类长寿中起作用。（C）2003年爱思唯尔公司。保留所有权利。
The human sirtuin 3 (SIRT3) gene encodes a putative mitochondrial NAD-dependent deacetylase (SIRT3) which belongs to the evolutionary conserved family of sirtuin 2 proteins. Studies in model organisms have demonstrated that SIR2 genes control lifespan, while no data are available regarding a possible role of SIRT3 in human longevity. By analysing the genotype-specific survival function relevant to the G477T marker of SIRT3, we found that in males the TT genotype increases (p = 0.0272), while the GT genotype decreases (p = 0.0391) survival in the elderly. Since SIRT3 lies in a chromosomal region (11p15.5) where four genes potentially associated with longevity are located (HRAS1, Insulin-like Growth Factor 2, Proinsulin, and Tyrosine Hydroxylase) we tested for linkage-disequilibrium between G477T alleles and alleles of the above genes. The disequilibrium was not significant in any case, thus suggesting that SIRT3 itself, or a gene strictly linked to SIRT3, may have a role in human longevity. (C) 2003 Elsevier Inc. All rights reserved.