title: Association study on long-living individuals from Southern Italy identifies rs10491334 in the CAMKIV gene that regulates survival proteins.
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.
authors: Dipartimento di Informatica e Sistemistica, Università degli Studi di Pavia, Pavia, Italy.
authors: Alberto
authors: A
authors: Malovini
authors: Maddalena
authors: M
authors: Illario
authors: Guido
authors: G
authors: Iaccarino
authors: Francesco
authors: F
authors: Villa
authors: Anna
authors: A
authors: Ferrario
authors: Roberta
authors: R
authors: Roncarati
authors: Chiara Viviani
authors: CV
authors: Anselmi
authors: Valeria
authors: V
authors: Novelli
authors: Ersilia
authors: E
authors: Cipolletta
authors: Eleonora
authors: E
authors: Leggiero
authors: Alessandro
authors: A
authors: Orro
authors: Maria Rosaria
authors: MR
authors: Rusciano
authors: Luciano
authors: L
authors: Milanesi
authors: Angela Serena
authors: AS
authors: Maione
authors: Gianluigi
authors: G
authors: Condorelli
authors: Riccardo
authors: R
authors: Bellazzi
authors: Annibale A
authors: AA
authors: Puca