Association study on long-living individuals from southern Italy Identifies rs10491334 in the CAMKIV gene that regulates survival proteins

Alberto Malovini, Maddalena Illario, Guido Iaccarino, Francesco Villa, Anna Ferrario, Roberta Roncarati, Chiara Viviani Anselmi, Valeria Novelli, Ersilia Cipolletta, Eleonora Leggiero, Alessandro Orro, Maria Rosaria Rusciano, Luciano Milanesi, Angela Serena Maione, Gianluigi Condorelli, Riccardo Bellazzi, Annibale A. Puca

Research output: Contribution to journalArticle

Abstract

Long-living individuals (LLIs) are used to study exceptional longevity. A number of genetic variants have been found associated in LLIs to date, but further identification of variants would improve knowledge on the mechanisms regulating the rate of aging. Therefore, we performed a genome-wide association study on 410 LLIs and 553 young control individuals with a 317K single-nucleotide polymorphism (SNP) chip to identify novel traits associated with aging. Among the top (p <1 × 10 -4) SNPs initially identified, we found rs10491334 (CAMKIV) (odds ratio [OR] = 0.55; 95% confidence interval [CI] 0.42-0.73; p = 2.88 × 10 -5), a variant previously reported associated with diastolic blood pressure, associated also in a replication set of 116 LLIs and 160 controls (OR = 0.54; 95% CI 0.32-0.90; p = 9 × 10 -3). Furthermore, in vitro analysis established that calcium/calmodulin-dependent protein kinase IV (CAMKIV) activates the survival proteins AKT, SIRT1, and FOXO3A, and we found that homozygous carriers of rs10491334 have a significant reduction in CAMKIV expression. This, together with the observed reduction in minor-allele carriers among centenarians, points to a detrimental role for the SNP. In conclusion, prolongevity genes are activated by CAMKIV, the levels of which are influenced by rs10491334, a SNP associated with human longevity.

Original languageEnglish
Pages (from-to)283-291
Number of pages9
JournalRejuvenation Research
Volume14
Issue number3
DOIs
Publication statusPublished - Jun 1 2011

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ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

Cite this

Malovini, A., Illario, M., Iaccarino, G., Villa, F., Ferrario, A., Roncarati, R., Anselmi, C. V., Novelli, V., Cipolletta, E., Leggiero, E., Orro, A., Rusciano, M. R., Milanesi, L., Maione, A. S., Condorelli, G., Bellazzi, R., & Puca, A. A. (2011). Association study on long-living individuals from southern Italy Identifies rs10491334 in the CAMKIV gene that regulates survival proteins. Rejuvenation Research, 14(3), 283-291. https://doi.org/10.1089/rej.2010.1114