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

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 50 years 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 N 25) over two follow-up surveys 10 years apart to have a negative association between SDNN, calculated as geometric means, with BMI. The examined NFE2L2 variant sustainably modified (p(interaction) = 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. (C) 2016 Swiss Tropical and Public Health Institute. Published by Elsevier Ireland Ltd.