Plasma dihydroceramide species associate with waist circumference in Mexican American families

Abstract

Objective: Waist circumference (WC), the clinical marker of central obesity, is gaining popularity as a screening tool for type 2 diabetes (T2D). While there is epidemiologic evidence favoring the WC-T2D association, its biological substantiation is generally weak. Our objective was to determine the independent association of plasma lipid repertoire with WC.

Methods: Samples and data from the San Antonio Family Heart Study of 1208 Mexican Americans from 42 extended families were used. Association of plasma lipidomic profiles with the cross-sectionally assessed WC was determined. Plasma lipidomic profiling entailed liquid chromatography with mass spectrometry. Statistical analyses included multivariable polygenic regression models and bivariate trait analyses using the SOLAR software.

Results: After adjusting for age and sex interactions, body mass index, homeostasis model of assessment-insulin resistance, total cholesterol, triglycerides, high density lipoproteins and use of lipid lowering drugs, dihydroceramides as a class were associated with WC. Dihydroceramide species 18:0, 20:0, 22:0, and 24:1 were significantly associated and genetically correlated with WC. Two sphingomyelin species (31:1 and 41:1) were also associated with WC.

Conclusions: Plasma dihydroceramide levels independently associate with WC. Thus, high resolution plasma lipidomic studies can provide further credence to the biological underpinnings of the association of WC with T2D.

Figure 1. Statistical method used to study the association of a class of lipids with a phenotypic trait

A lipid class is a collection of s lipid species (rectangle on the left). For a given lipid class, three models (M₁, M₂ and M₃ described in a tabular format on the right) were run and log-likelihoods from these three models were used as shown at the bottom to estimate the mean effect, its statistical significance and heterogeneity of within-class associations. For details, refer to text.

Figure 2. Associations of the lipid classes with WC

The strength of the association of each lipid class is shown as z-score (the class-specific regression coefficient divided by its standard error) estimated from polygenic regression models and the statistical significance of this association is indicated by the asterisk on the right.