TY - JOUR
T1 - Association study on long-living individuals from southern Italy Identifies rs10491334 in the CAMKIV gene that regulates survival proteins
AU - Malovini, Alberto
AU - Illario, Maddalena
AU - Iaccarino, Guido
AU - Villa, Francesco
AU - Ferrario, Anna
AU - Roncarati, Roberta
AU - Anselmi, Chiara Viviani
AU - Novelli, Valeria
AU - Cipolletta, Ersilia
AU - Leggiero, Eleonora
AU - Orro, Alessandro
AU - Rusciano, Maria Rosaria
AU - Milanesi, Luciano
AU - Maione, Angela Serena
AU - Condorelli, Gianluigi
AU - Bellazzi, Riccardo
AU - Puca, Annibale A.
PY - 2011/6/1
Y1 - 2011/6/1
N2 - 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.
AB - 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.
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U2 - 10.1089/rej.2010.1114
DO - 10.1089/rej.2010.1114
M3 - Article
C2 - 21612516
AN - SCOPUS:79960352048
VL - 14
SP - 283
EP - 291
JO - Rejuvenation Research
JF - Rejuvenation Research
SN - 1549-1684
IS - 3
ER -