title: The adverse impact of obesity on heart rate variability is modified by a NFE2L2 gene variant: The SAPALDIA cohort.
abstract: BACKGROUND
  Overweight has been associated with an increase in inflammatory markers and with an imbalance in the autonomic nervous system, such as a decrease in heart rate variability (HRV). In this study we aimed to investigate the modifying effect of a genetic variation in a major anti-inflammatory marker gene, NFE2L2, on the relationship between overweight and HRV.
  
  
  METHODS
  We analyzed participants of the SAPALDIA cohort aged 50years and older, twice in 2002/2003 (N=1472) and 2010/2011 (N=1235). We included persons with valid genotype data, who underwent ambulatory 24-h electrocardiogram monitoring, and reported on medical history and lifestyle. The association between HRV and BMI, measured as standard deviation of normal-to-normal intervals (SDNN) by BMI and the modifying effect of the cardiovascular health-related NFE2L2 gene variant rs2364723 were tested, applying multivariable mixed linear regression models.
  
  
  RESULTS
  We found study participants with overweight (BMI>25) over two follow-up surveys 10years apart to have a negative association between SDNN, calculated as geometric means, with BMI. The examined NFE2L2 variant sustainably modified (pinteraction=0.014) the found inverse association between a BMI increment and SDNN, causing a stronger decrement in SDNN for participants with the CC genotype (-20.7%; 95%-confidence interval: -12.33 to -28.28) compared with participants carrying the GC (-7.43; 95%CI: -3.56 to -11.15) or GG (-11.26%; 95%CI: -7.68 to -14.7) genotype, estimated for the difference from the 90thto the 10thpercentile of BMI by the NFE2L2 variant.
  
  
  CONCLUSIONS
  Our results are consistent with the hypothesis that overweight decreases heart rate variability through inflammatory processes.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: martin.adam@unibas.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Adam
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: medea.imboden@unibas.ch.
authors.forename: Medea
authors.initials: M
authors.lastname: Imboden
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: emmanuel.schaffner@unibas.ch.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Schaffner
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Boes
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: florian.kronenberg@i-med.ac.at.
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.affiliation: Division of Pulmonary Medicine, Regional Hospital of Lugano, Lugano, Switzerland. Electronic address: marco.pons@eoc.ch.
authors.forename: Marco
authors.initials: M
authors.lastname: Pons
authors.affiliation: Lungenzentrum, Hirslanden Klinik Aarau, Aarau, Switzerland. Electronic address: robert.bettschart@hin.ch.
authors.forename: Robert
authors.initials: R
authors.lastname: Bettschart
authors.affiliation: Laboratory SNA-EPIS EA4607, Department of Physiology, University Hospital of Saint-Etienne, PRES Lyon, France. Electronic address: jc.barthelemy@univ-st-etienne.fr.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Barthelemy
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: christian.schindler@unibas.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: nicole.probst@unibas.ch.
authors.forename: Nicole
authors.initials: N
authors.lastname: Probst-Hensch
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality / Q000503:physiopathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004562:Electrocardiography / Q000379:methods; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D050177:Overweight / Q000150:complications / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D015996:Survival Rate
chemical_list: D051267:NF-E2-Related Factor 2
keywords: Autonomic nervous system; Heart rate variability; Inflammation; Obesity; Polymorphism genetics