Association of Α-Klotho and Blood Lead and Cadmium: A Cross-Sectional Study

Abstract

Epigenetic aging is associated with harmful health effects such as oxidative stress from heavy metal exposure. We considered about the relationship between genes and heavy metals associated with oxidative stress, then investigated the association between serum klotho and lead and cadmium exposure among adults in the United States from 2007 to 2016 through National Health and Nutrition Examination Survey (NHANES). Samples were 8,311 adults aged 40 to 79 years with measurements of serum α-klotho, blood lead and cadmium, and complete covariate data. Blood lead and cadmium levels were measured inductively coupled plasma mass spectrometry from a one-half sample of NHANES participants aged 12 years and older. Serum α-klotho levels were measured among adults aged 40 to 79 years using enzyme-linked immunosorbent assay (ELISA). Multivariate linear regression analysis was used to estimate the association between serum α-klotho and blood lead and cadmium levels. The estimated beta coefficients of log-transformed α-klotho per unit increase in log-transformed blood lead and cadmium levels were -0.0502 (0.0085; p < 0.0001) and -0.0181 (0.0054; p < 0.0001), respectively. Even after adjustment, the relationship remained significant for both lead (β= -0.0416, SE=0.0091; p < 0.0001) and cadmium (β= -0.0148, SE=0.0071; p < 0.0427). Compared with quartile 1 as the reference, the fully-adjusted beta coefficients for quartiles 2, 3, and 4 of log-transformed lead were -0.0148 (SE=0.0091; p = 0.2556), -0.0353 (SE=0.0156; p = 0.0272), and -0.0655 (SE=0.0157; p < 0.0001) respectively. Comparing quartiles 2, 3, and 4 of cadmium with the lowest quartile, fully-adjusted beta coefficients were 0.0049 (SE=0.0118; p = 0.6799), -0.0011 (SE=0.0130; p = 0.9305), and -0.0265 (SE=0.0153; p = 0.0890), respectively. Blood lead and cadmium levels were negatively associated with serum α-klotho levels in a representative population of US adults. Further research is recommended to investigate the causality behind such relationship.

Keywords: heavy metal, Lead, cadmium, klotho, public health, aging