title: Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline.
abstract: Lung function is an independent predictor of mortality and serves as an aging marker in never smokers. The protein sirtuin-1 of gene SIRT1 has profound anti-inflammatory effects and regulates metabolic pathways. Its suggested longevity effects on lower organisms remain poorly studied in humans. In 1132 never smokers of the population-based SAPALDIA cohort, we investigated associations between single nucleotide polymorphisms (SNPs; rs730821, rs10997868, rs10823116) of SIRT1 and aging-related lung function decline over 11 years in terms of change in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25 and 75 % of FVC (FEF25-75) using multiple linear regression models. Interactions between the SIRT1 SNPs and adiposity parameters (body mass index (BMI), its change and weight gain) were tested by including multiplicative interaction terms into the models. SIRT1 polymorphisms exhibited no main effects, but modified the association between obesity measures and FEV1/FVC and FEF25-75 decline (p = 0.009-0.046). Per risk allele, FEV1/FVC decline was accelerated up to -0.5 % (95 % CI -1.0 to 0 %) and -0.7 % (-1.3 to -0.2 %) over interquartile range increases in BMI (2.4 kg/m(2)) or weight (6.5 kg), respectively. For FEF25-75 decline, corresponding estimates were -57 mL/s (-117 to 4 mL/s) and -76 mL/s (-1429 to -9 mL/s). Interactions were not present in participants with genetically lowered C-reactive protein concentrations. Genetic variation in SIRT1 might therefore affect lung function and human longevity by modifying subclinical inflammation arising from abdominal adipose tissue.
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland. ivan.curjuric@unibas.ch.|University of Basel, Basel, Switzerland. ivan.curjuric@unibas.ch.
authors.forename: Ivan
authors.initials: I
authors.lastname: Curjuric
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Medea
authors.initials: M
authors.lastname: Imboden
authors.affiliation: Division of Pulmonary Medicine, University Hospitals, Geneva, Switzerland.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Bridevaux
authors.affiliation: Division of Pulmonary Medicine, University Hospitals, Geneva, Switzerland.
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Gerbase
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Margot
authors.initials: M
authors.lastname: Haun
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Dirk
authors.initials: D
authors.lastname: Keidel
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.|University of Basel, Basel, Switzerland.|Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ashish
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Division of Pulmonary Medicine, Regional Hospital of Lugano, Lugano, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Pons
authors.affiliation: Division of Pulmonary Medicine, University Hospitals, Geneva, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Rochat
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.|University of Basel, Basel, Switzerland.|Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Schikowski
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
authors.affiliation: Institute for Clinical Chemistry, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Probst-Hensch
mesh_terms: D050153:Abdominal Fat / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000375:Aging; D015992:Body Mass Index; D004247:DNA / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008171:Lung Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014797:Vital Capacity / Q000502:physiology*; D055815:Young Adult
chemical_list: D004247:DNA; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Cohort study; Inflammation; Lung; Metabolism; Population-based; Sirtuin-1