title: Association analysis of the SHC1 gene locus with longevity in the Japanese population.
abstract: 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.
authors.affiliation: Human Genome Research Group, RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kamei
authors.forename: Naoki
authors.initials: N
authors.lastname: Adati
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamura
authors.forename: Michiyo
authors.initials: M
authors.lastname: Takayama
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakazawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ebihara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gondo
authors.forename: Mizuho
authors.initials: M
authors.lastname: Akechi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Noguchi
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hirose
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Kojima
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D004247:DNA / Q000235:genetics; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008136:Longevity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D004247:DNA