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Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline.

  • Curjuric I Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland. ivan.curjuric@unibas.ch.
  • Imboden M Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.
  • Bridevaux PO Division of Pulmonary Medicine, University Hospitals, Geneva, Switzerland.
  • Gerbase MW Division of Pulmonary Medicine, University Hospitals, Geneva, Switzerland.
  • Haun M Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
  • Keidel D Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.
  • Kumar A Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.
  • Pons M Division of Pulmonary Medicine, Regional Hospital of Lugano, Lugano, Switzerland.
  • Rochat T Division of Pulmonary Medicine, University Hospitals, Geneva, Switzerland.
  • Schikowski T Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.
  • Schindler C Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.
  • von Eckardstein A Institute for Clinical Chemistry, University Hospital Zürich, Zürich, Switzerland.
  • Kronenberg F Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
  • Probst-Hensch NM Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, P.O. Box, 4002, Basel, Switzerland.
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  • 2016-04-30
Published in:
  • Age (Dordrecht, Netherlands). - 2016
Cohort study
Inflammation
Lung
Metabolism
Population-based
Sirtuin-1
Abdominal Fat
Adolescent
Adult
Aging
Body Mass Index
DNA
Female
Follow-Up Studies
Forced Expiratory Volume
Genotype
Humans
Lung
Lung Diseases
Male
Middle Aged
Polymorphism, Single Nucleotide
Retrospective Studies
Sirtuin 1
Time Factors
Vital Capacity
Young Adult
English 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/263468
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