Association of Serum Total Bilirubin Concentration with Telomere Length: The National Health and Nutrition Examination Survey

Abstract

Introduction. Mildly increased bilirubin concentration has a protective effect on oxidative stress–related diseases. However, it remains unknown whether elevated circulating bilirubin is associated with longer telomere length. The aim of this cross-sectional study was to examine the association between total bilirubin concentration and telomere length. Methods. We used the data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The multivariable linear regression model was used to examine the association between total bilirubin concentration and telomere length. The nonlinear relationship was analyzed using a generalized additive model with the smoothing plot. Results. A total of 7818 participants with a mean age of $49.20\pm 18.82$ years were included. Compared with the lowest concentration of total bilirubin (Q1), the highest quartile of total bilirubin concentration was associated with longer telomere length in male ( $\beta =0.04$ , 95 CI%: 0.00, 0.07, $P=0.024$ ) and female ( $\beta =0.04$ , 95 CI%: 0.02, 0.04, $P=0.002$ ). Furthermore, an inverted U-shaped relationship between total bilirubin and telomere length was found. On the left of turning points ( $\text{total}\text{bilirubin}<0.5\text{mg}/\text{dL}$ ), total bilirubin concentration was positively associated with telomere length ( $\beta =0.23$ , 95 CI%: 0.14, 0.32, $P<0.001$ ). However, the association between total bilirubin concentration and telomere length was not significant ( $\beta =0.01$ , 95% CI: -0.01, 0.04, $P=0.346$ ) above the turning point. Conclusion. This is the first evidence based on a nationally representative survey demonstrating a positive and nonlinear association between total bilirubin concentration and telomere length. Future large-scale prospective studies are warranted to confirm our findings.