AGE

, Volume 35, Issue 4, pp 1357–1366 | Cite as

MAP3K7 and GSTZ1 are associated with human longevity: a two-stage case–control study using a multilocus genotyping

  • Fausta Di Cianni
  • Daniele Campa
  • Federica Tallaro
  • Cosmeri Rizzato
  • Francesco De Rango
  • Roberto Barale
  • Giuseppe Passarino
  • Federico Canzian
  • Federica Gemignani
  • Alberto Montesanto
  • Stefano Landi
  • Giuseppina Rose
Article

Abstract

The pathways that regulate energy homeostasis, the mechanisms of damage repair, and the signaling response to internal environmental changes or external signals have been shown to be critical in modulating lifespan of model organisms and humans. In order to investigate whether genetic variation of genes involved in these pathways contribute to longevity, a two-stage case–control study in two independent sets of long-lived individuals from Calabria (Italy) was performed. In stage 1, 317 SNPs in 104 genes were analyzed in 78 cases (median age 98 years) and 71 controls (median age 67 years). In stage 2, 31 candidate SNPs identified in stage 1 (πmarkers = 0.1) were analyzed in an independent sample composed by 288 cases (median age 92 years) and 554 controls (median age 67 years). Two SNPs, rs282070 located in intron 1 of the MAP3K7 gene, and rs2111699 located in intron 1 of the GSTZ1 gene, were significantly associated (after adjustment for multiple testing) with longevity in stage 2 (p = 1.1 × 10−3 and p = 1.4 × 10−3, respectively). Interestingly, both genes are implicated in the cellular response to internal and external environmental changes, playing a crucial role in the inflammation processes that accompany aging. Our data confirm that long-lived subjects are endowed with genetic variants that allow them to optimize these cellular responses and to better deal with environmental and internal stresses.

Keywords

Longevity Two-stage analysis Single-nucleotide polymorphisms Multilocus 

Supplementary material

11357_2012_9416_MOESM1_ESM.doc (730 kb)
Table S1Loci and polymorphisms analyzed in stage 1 (DOC 729 kb)
11357_2012_9416_MOESM2_ESM.doc (104 kb)
Table S2Top-ranked SNPs (πmarkers = 0.1) obtained according to \( {\chi^{{2}}}_{\text{MAX}} \) test in the stage 1 sample (DOC 104 kb)
11357_2012_9416_MOESM3_ESM.doc (88 kb)
Table S3Association results of the 29 selected SNPs ranked on the basis of their estimated p values obtained according to \( {\chi^{{2}}}_{\text{MAX}} \) test in the stage 2 sample (DOC 88 kb)
11357_2012_9416_MOESM4_ESM.doc (72 kb)
Table S4Interaction analysis results obtained using the Model-Based Multifactor Dimensionality Reduction approach proposed by Calle et al. (2010) (DOC 71 kb)

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Copyright information

© American Aging Association 2012

Authors and Affiliations

  • Fausta Di Cianni
    • 1
  • Daniele Campa
    • 2
  • Federica Tallaro
    • 1
  • Cosmeri Rizzato
    • 2
  • Francesco De Rango
    • 1
  • Roberto Barale
    • 3
  • Giuseppe Passarino
    • 1
  • Federico Canzian
    • 2
  • Federica Gemignani
    • 3
  • Alberto Montesanto
    • 1
  • Stefano Landi
    • 3
  • Giuseppina Rose
    • 1
  1. 1.Department of Cell BiologyUniversity of CalabriaRendeItaly
  2. 2.Genomic Epidemiology GroupGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Department of BiologyUniversity of PisaPisaItaly

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