title: The SIRT1 promoter polymorphic site rs12778366 increases IL-6 related human mortality in the prospective study "Treviso Longeva (TRELONG)".
abstract: Studies on sirtuins (SIRT), a family of proteins with deacetylase activity, have provided convergent evidence of the key role of these enzymes in aging-linked physiological functions. The link between SIRT1 and longevity has emerged in model organism but few data are available in humans, in particular relying on longitudinal studies. Here, we assessed whether a genetic variant within SIRT1 gene promoter (rs12778366) was associated to human longevity. We analyzed 586 genomic DNA (gDNA) collected in the study "Treviso Longeva" (TRELONG), including elderly over 70 years of age from the municipality of Treviso, a town in the Northeast of Italy, with a 11-year follow-up. We genotyped SIRT1 rs12778366 by real-time polymerase chain reaction (RT-PCR) allelic discrimination assay. A cross-sectional analysis performed by comparing people over and under 85 years of age did not evidence association between rs12778366 and longevity. When we performed a longitudinal analysis considering mortality as dependent variable, we did not observe an association of rs12778366 with longevity in the whole population (corrected P-value = 0.33). However, when we stratified the TRELONG subjects according to circulating level of interleukin-6 (IL-6), a predictor of disability and mortality, we found that rs12778366 (TC+CC) carriers were at increased risk of mortality in comparison to the TT reference group (corrected P-value = 0.03, HR 1.47). Our data do not support a major role of rs12778366 in human longevity, but the stratified analysis on IL-6 suggests that this variant may be involved in the detrimental effect of high circulating IL-6 in the elderly.
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" via La Masa 19, Milan I-20156, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
authors.affiliation: Department of Statistics, University of Padova Via Cesare Battisti, 241, Padova I-35121, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mazzuco
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" via La Masa 19, Milan I-20156, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Chierchia
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" via La Masa 19, Milan I-20156, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Fusco
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" via La Masa 19, Milan I-20156, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Boeri
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" via La Masa 19, Milan I-20156, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Martines
authors.affiliation: South Health District, Local Health Authority n. 9 of Treviso Via Isola di Mezzo, 37, Treviso I-31100, Italy.
authors.forename: Enrico Di
authors.initials: ED
authors.lastname: Giorgi
authors.affiliation: Department of Transfusional Medicine, General Hospital of Treviso Piazza Ospedale, 1, Treviso I-31100, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Frigato
authors.affiliation: Department of Transfusional Medicine, General Hospital of Treviso Piazza Ospedale, 1, Treviso I-31100, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Durante
authors.affiliation: Department of Clinical Pathology, General Hospital of Treviso Piazza Ospedale, 1, Treviso I-31100, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Caberlotto
authors.affiliation: Department of Clinical Pathology, General Hospital of Treviso Piazza Ospedale, 1, Treviso I-31100, Italy ; FORGEI, Interdisciplinary Geriatric Research Foundation Viale Trento Trieste 19, Treviso I-31100, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanardo
authors.affiliation: Department of Clinical Pathology, General Hospital of Treviso Piazza Ospedale, 1, Treviso I-31100, Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Siculi
authors.affiliation: South Health District, Local Health Authority n. 9 of Treviso Via Isola di Mezzo, 37, Treviso I-31100, Italy ; FORGEI, Interdisciplinary Geriatric Research Foundation Viale Trento Trieste 19, Treviso I-31100, Italy ; Cognitive Impairment Centre, General Hospital of Treviso Piazza Ospedale, 1, Treviso I-31100, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gallucci
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" via La Masa 19, Milan I-20156, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
keywords: SIRT1; genetics; longevity; prospective study; rs12778366