Genetic control of the HDL proteome

Nathalie Pamir; Calvin Pan; Deanna L. Plubell; Patrick M. Hutchins; Chongren Tang; Jake Wimberger; Angela Irwin; Thomas Q. de Aguiar Vallim; Jay W. Heinecke; Aldons J. Lusis

Correlation networks such as weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes. The weighted correlation network analysis (WGCNA), revealed that core HDL proteins, composed of most common apoproteins are highly correlated and co-regulated. The co-regulated gene network is consistent with HDL's role in innate immunity and lipid metabolism as it reveals a tight network of co-regulation among the proteins with primary roles in immunity and lipid metabolism. The histocompatibility protein isoforms such as H2Q4 and H2-Q10 that have been shown to be associated with mouse HDL in multiple studies (S. M. Gordon et al., 2010; Pamir et al., 2016) are part of the core co-regulated proteins. In mice, histocompatibility proteins play a role in innate immunity by antigen presenting via major histocompatibility complex class 1 (MHC-1).H2-Q10 is the only murine MHC-1 protein found in the serum in appreciable concentrations (Lew et al., 1986) . While these innate immune proteins with roles in antigen presentation are part of core co-regulation network, acute phase proteins such SAA1 and SAA2 are not, as they are primarily regulated by an inflammatory stimulus.