The adverse impact of obesity on heart rate variability is modified by a NFE2L2 gene variant: The SAPALDIA cohort

Int J Cardiol. 2017 Feb 1:228:341-346. doi: 10.1016/j.ijcard.2016.11.049. Epub 2016 Nov 8.

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 90th to the 10th percentile of BMI by the NFE2L2 variant.

Conclusions: Our results are consistent with the hypothesis that overweight decreases heart rate variability through inflammatory processes.

Keywords: Autonomic nervous system; Heart rate variability; Inflammation; Obesity; Polymorphism genetics.

MeSH terms

  • Aged
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology*
  • Cohort Studies
  • Cross-Sectional Studies
  • Electrocardiography / methods
  • Female
  • Genetic Variation*
  • Genotype
  • Heart Rate / genetics*
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • NF-E2-Related Factor 2 / genetics*
  • Obesity / complications
  • Obesity / physiopathology*
  • Overweight / complications
  • Overweight / physiopathology
  • Polymorphism, Genetic*
  • Prognosis
  • Risk Assessment
  • Survival Rate

Substances

  • NF-E2-Related Factor 2