Association study on long-living individuals from Southern Italy identifies rs10491334 in the CAMKIV gene that regulates survival proteins.

Authors:
Alberto Malovini
Alberto Malovini
University of Pavia
Maddalena Illario
Maddalena Illario
University of Naples Federico II
Napoli | Italy
Prof. Guido Iaccarino, MD, PhD
Prof. Guido Iaccarino, MD, PhD
Federico II University of Naples
Full Professor of Applied Medical Science and Technology
Cardiology
Napoli, Campania | Italy
Francesco Villa
Francesco Villa
St. Georges Hospital
United Kingdom
Roberta Roncarati
Roberta Roncarati
Albert Einstein College of Medicine
United States
Chiara Viviani Anselmi
Chiara Viviani Anselmi
Unit of Genetics and Cardiovascular Research Institute
Italy
Valeria Novelli
Valeria Novelli
NYU School of Medicine
Italy

Rejuvenation Res 2011 Jun 25;14(3):283-91. Epub 2011 May 25.

Dipartimento di Informatica e Sistemistica, Università degli Studi di Pavia, Pavia, Italy.

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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http://dx.doi.org/10.1089/rej.2010.1114DOI Listing

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June 2011
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