title: MAP3K7 and GSTZ1 are associated with human longevity: a two-stage case-control study using a multilocus genotyping.
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 (π markers = 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.
authors.affiliation: Department of Cell Biology, University of Calabria, 87036, Rende, Italy.
authors.forename: Fausta
authors.initials: F
authors.lastname: Di Cianni
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
authors.forename: Federica
authors.initials: F
authors.lastname: Tallaro
authors.forename: Cosmeri
authors.initials: C
authors.lastname: Rizzato
authors.forename: Francesco
authors.initials: F
authors.lastname: De Rango
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
authors.forename: Alberto
authors.initials: A
authors.lastname: Montesanto
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rose
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007558:Italy; D008136:Longevity / Q000235:genetics*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D004247:DNA; D005982:Glutathione Transferase; D020930:MAP Kinase Kinase Kinases; D000099151:MAP Kinase Kinase Kinase 7; C407705:GSTZ1 protein, human