Kamei Hidehiko, Adati Naoki, Arai Yasumichi, Yamamura Ken, Takayama Michiyo, Nakazawa Susumu, Ebihara Yoshinori, Gondo Yasuyuki, Akechi Mizuho, Noguchi Toshihide, Hirose Nobuyoshi, Sakaki Yoshiyuki, Kojima Toshio
Human Genome Research Group, RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
J Mol Med (Berl). 2003 Nov;81(11):724-8. doi: 10.1007/s00109-003-0485-0. Epub 2003 Oct 2.
The SHC1 gene encodes a signaling and transforming protein that has been implicated in the aging process in worms and mammals. In this study we examined 230 Japanese centenarians and 180 healthy younger controls and looked at the SHC1 locus as a candidate region that may be associated with longevity. We identified 12 single nucleotide polymorphisms (SNPs) within a 10-kb region encompassing the entire SHC1 gene from the DNA of 30 centenarians and 24 healthy younger controls. Five SNPs, including three nonsynonymous sites, lay within coding elements, six were located within introns, and one was in the 3' untranslated region. All of these SNPs were relatively rare, with a minor allele frequency of less than 5% in our subjects. A pairwise linkage disequilibrium analysis using the r2 statistic showed that two of the SNP pairs are in tight linkage disequilibrium at this locus. We investigated the possible association of SHC1 with longevity using association analyses with allelotypes and haplotypes but found that the SNPs identified in SHC1 had no impact on longevity for Japanese centenarians.
SHC1基因编码一种信号传导和转化蛋白，该蛋白与蠕虫和哺乳动物的衰老过程有关。在本研究中，我们检测了230名日本百岁老人和180名健康的年轻对照者，并将SHC1基因座视为可能与长寿相关的候选区域。我们从30名百岁老人和24名健康年轻对照者的DNA中，在一个包含整个SHC1基因的10kb区域内鉴定出12个单核苷酸多态性（SNP）。其中5个SNP，包括3个非同义位点，位于编码元件内，6个位于内含子内，1个位于3'非翻译区。所有这些SNP相对罕见，在我们的研究对象中次要等位基因频率低于5%。使用r2统计量进行的成对连锁不平衡分析表明，在该基因座上有两对SNP处于紧密连锁不平衡状态。我们通过对单倍型和单倍体进行关联分析，研究了SHC1与长寿之间可能的关联，但发现SHC1中鉴定出的SNP对日本百岁老人的长寿没有影响。
