Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study.

Authors: Stessman J; Maaravi Y; Hammerman-Rozenberg R; Cohen A; Nemanov L; Gritsenko I; Gruberman N; Ebstein RP

Abstract: In an exploratory study, 11 common polymorphisms were examined for contributing to longevity including: apolipoprotein E (apoE), methylenetetrahydrofolate reductase (MTHFR), cathepsin D (CAD), superoxide dismutase 2 (SOD2), angiotensinogen (AGT) and insulin-like growth factor 2 (IGF2), Leiden factor 7, p53 oncogene, dopamine D4 receptor (DRD4) and the serotonin transporter (SERT). Genotype and allele frequencies of these genes were compared in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity to a group of 441 younger subjects (22 years). Nominally significant results provide suggestive evidence in the Ashkenazi group that apoE, MHTFR, SOD2, IGF2 ApaI, and factor VII are risk factors for a single outcome, survival to 75. Overall, the more genetically homogenous Ashkenazi ethnic group showed evidence for association in five genes examined suggesting that future studies in this population would gainfully focus on this ethnic group.

Keywords: Adolescent; Adult; Age Factors; Aged; Aging/ethnology/*genetics; Angiotensinogen/genetics; Apolipoproteins E/genetics; Cathepsin D/genetics; DNA Primers/genetics; Factor VII/genetics; Female; Genes, p53/genetics; Genetic Linkage; Genotype; Humans; Insulin/metabolism; Insulin-Like Growth Factor II/genetics; Israel; Life Expectancy; Longevity/*genetics; Longitudinal Studies; Male; Membrane Glycoproteins/genetics; Membrane Transport Proteins/genetics; Methylenetetrahydrofolate Reductase (NADPH2)/genetics; Middle Aged; Nerve Tissue Proteins/genetics; *Polymorphism, Genetic; Receptors, Dopamine D2/genetics; Receptors, Dopamine D4; Risk Factors; Serotonin Plasma Membrane Transport Proteins; Superoxide Dismutase/genetics
Journal: Mechanisms of ageing and development
Volume: 126
Issue: 2
Pages: 333-9
Date: Dec. 29, 2004
PMID: 15621215
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Stessman J, Maaravi Y, Hammerman-Rozenberg R, Cohen A, Nemanov L, Gritsenko I, Gruberman N, Ebstein RP (2005) Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study. Mechanisms of ageing and development 126: 333-9.

Lifespan Factors:
  • IGF2 insulin-like growth factor 2 (somatomedin A)
  • APOE apolipoprotein E

  • Longevity Variant Associations (p-value):
  • APOE e2,e3,e4 (0.01)
  • CTSD (1.0)
  • ApaI (0.063)
  • rs4880 (0.009)
  • rs1801133 (0.014)
  • R353Q (0.045)
  • AGT (1.0)
  • TP53 (1.0)
  • DRD4 (1.0)
  • SLC6A4 (1.0)
  • rs429358, rs7412 (0.025)
  • rs1801133 (0.029)
  • -
  • rs4880 (0.009)
  • -
  • A/G (0.063)
  • -
  • -
  • -
  • - (0.045)

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