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Genetic correlation of the plasma lipidome with type 2 diabetes, prediabetes and insulin resistance in Mexican American families.

ABSTRACT: Differential plasma concentrations of circulating lipid species are associated with pathogenesis of type 2 diabetes (T2D). Whether the wide inter-individual variability in the plasma lipidome contributes to the genetic basis of T2D is unknown. Here, we investigated the potential overlap in the genetic basis of the plasma lipidome and T2D-related traits.We used plasma lipidomic data (1202 pedigreed individuals, 319 lipid species representing 23 lipid classes) from San Antonio Family Heart Study in Mexican Americans. Bivariate trait analyses were used to estimate the genetic and environmental correlation of all lipid species with three T2D-related traits: risk of T2D, presence of prediabetes and homeostatic model of assessment - insulin resistance. We found that 44 lipid species were significantly genetically correlated with one or more of the three T2D-related traits. Majority of these lipid species belonged to the diacylglycerol (DAG, 17 species) and triacylglycerol (TAG, 17 species) classes. Six lipid species (all belonging to the triacylglycerol class and containing palmitate at the first position) were significantly genetically correlated with all the T2D-related traits.Our results imply that: a) not all plasma lipid species are genetically informative for T2D pathogenesis; b) the DAG and TAG lipid classes partially share genetic basis of T2D; and c) 1-palmitate containing TAGs may provide additional insights into the genetic basis of T2D.

SUBMITTER: Kulkarni H

PROVIDER: S-EPMC5438505 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other

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Genetic correlation of the plasma lipidome with type 2 diabetes, prediabetes and insulin resistance in Mexican American families.

Kulkarni Hemant H Mamtani Manju M Wong Gerard G Weir Jacquelyn M JM Barlow Christopher K CK Dyer Thomas D TD Almasy Laura L Mahaney Michael C MC Comuzzie Anthony G AG Duggirala Ravindranath R Meikle Peter J PJ Blangero John J Curran Joanne E JE

BMC genetics 20170519 1

<h4>Background</h4>Differential plasma concentrations of circulating lipid species are associated with pathogenesis of type 2 diabetes (T2D). Whether the wide inter-individual variability in the plasma lipidome contributes to the genetic basis of T2D is unknown. Here, we investigated the potential overlap in the genetic basis of the plasma lipidome and T2D-related traits.<h4>Results</h4>We used plasma lipidomic data (1202 pedigreed individuals, 319 lipid species representing 23 lipid classes) fr ...[more]

PMID: 28525987

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Project description:Introduction Cardiovascular disease (CVD) is the leading cause of mortality worldwide and is the leading cause of death in the US. Lipid dysregulation is a well-known precursor to metabolic diseases, including CVD. There is a growing body of literature that suggests MRI-derived epicardial fat volume, or epicardial adipose tissue (EAT) volume, is linked to the development of coronary artery disease. Interestingly, epicardial fat is also actively involved in lipid and energy homeostasis, with epicardial adipose tissue having a greater capacity for release and uptake of free fatty acids. However, there is a scarcity of knowledge on the influence of plasma lipids on EAT volume. Aim The focus of this study is on the identification of novel lipidomic species associated with CMRI-derived measures of epicardial fat in Mexican American individuals. Methods We performed lipidomic profiling on 200 Mexican American individuals. High-throughput mass spectrometry enabled rapid capture of precise lipidomic profiles, providing measures of 799 unique species from circulating plasma samples. Because of our extended pedigree design, we utilized a standard quantitative genetic linear mixed model analysis to determine whether lipids were correlated with EAT by formally testing for association between each lipid species and the CMRI epicardial fat phenotype. Results After correction for multiple testing using the FDR approach, we identified 135 lipid species showing significant association with epicardial fat. Of those, 131 lipid species were positively correlated with EAT, where increased circulating lipid levels were correlated with increased epicardial fat. Interestingly, the top 10 lipid species associated with an increased epicardial fat volume were from the deoxyceramide (Cer(m)) and triacylglycerol (TG) families. Deoxyceramides are atypical and neurotoxic sphingolipids. Triacylglycerols are an abundant lipid class and comprise the bulk of storage fat in tissues. Pathologically elevated TG and Cer(m) levels are related to CVD risk and, in our study, to EAT volume. Conclusion Our results indicate that specific lipid abnormalities such as enriched saturated triacylglycerols and the presence of toxic ceramides Cer(m) in plasma of our individuals could precede CVD with increased EAT volume.

Dataset Information

Genetic correlation of the plasma lipidome with type 2 diabetes, prediabetes and insulin resistance in Mexican American families.

Publications

Genetic correlation of the plasma lipidome with type 2 diabetes, prediabetes and insulin resistance in Mexican American families.

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