Gender-specific association between circulating serum Klotho and metabolic components in adults

Klotho plays a pivotal role in human aging. Metabolic syndrome (MetS) is composed of multiple conditions that are also risk factors for cardiovascular disease and diabetes. We try to discuss gender-specific differences in Klotho and the associations between Klotho and MetS components.

The National Health and Nutrition Examination Survey database from cycle 2015-2016 was analyzed. MetS was defined according to the 2005 updated criteria by the American Heart Association and National Heart Lung and Blood Institute. Gender-specific differences in serum Klotho, and associations between Klotho level and MetS components were examined.

A total of 2475 participants (40-79 years old) with comprehensive data were included (52% women). In general, lower Klotho was associated with advanced age, male sex, tobacco use, elevated triglycerides, renal insufficiency, inflammation, low estradiol, and low sex hormone-binding globulin (SHBG). The correlation between MetS and Klotho was more obvious in women, mainly in waist circumference and triglyceride. There were no gender-specific differences in the associations between Klotho and renal dysfunction, but multivariate linear regression analysis showed gender differences in other factors associated with Klotho. Estradiol, SHBG, high-density lipoprotein cholesterol (HDL), and high-sensitivity C-reactive protein (CRP) were associated with Klotho levels independent of age and renal function in men, whereas in women, Klotho was independently associated with triglycerides and white blood cell count.

Klotho levels had gender disparities regardless of age, renal function, and sex hormones. In the current cohort, triglycerides were the major component of MetS that was independently associated with serum Klotho levels, and the association was particularly seen in women. However, HDL was found to be the male-specific MetS component independently associated with Klotho.