The NFE2L2 gene variant rs2364723 significantly modified the inverse association between BMI and heart rate variability, causing a stronger SDNN decrement in the CC genotype (-20.7%) (P=0.014).
Cohort (n=1,472)
Does the NFE2L2 gene variant modify the association between overweight and heart rate variability in adults aged 50 and older?
The NFE2L2 gene variant rs2364723 modifies the negative impact of overweight on heart rate variability, suggesting an inflammatory mechanism linking obesity to autonomic imbalance.
Effect estimate: SDNN decrement (95% CI -12.33 to -28.28)
p-value: p=0.014
BackgroundOverweight 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.MethodsWe 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.ResultsWe found study participants with overweight (BMI > 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 (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.ConclusionsOur results are consistent with the hypothesis that overweight decreases heart rate variability through inflammatory processes.
Adam et al. (Tue,) conducted a cohort in Overweight and obesity (n=1,472). NFE2L2 gene variant rs2364723 (CC genotype) vs. GC or GG genotype was evaluated on Heart rate variability measured as standard deviation of normal-to-normal intervals (SDNN) (SDNN decrement, 95% CI -12.33 to -28.28, p=0.014). The NFE2L2 gene variant rs2364723 significantly modified the inverse association between BMI and heart rate variability, causing a stronger SDNN decrement in the CC genotype (-20.7%) (P=0.014).