title: Genomics of post-prandial lipidomic phenotypes in the Genetics of Lipid lowering Drugs and Diet Network (GOLDN) study.
abstract: BACKGROUND
  Increased postprandial lipid (PPL) response to dietary fat intake is a heritable risk factor for cardiovascular disease (CVD). Variability in postprandial lipids results from the complex interplay of dietary and genetic factors. We hypothesized that detailed lipid profiles (eg, sterols and fatty acids) may help elucidate specific genetic and dietary pathways contributing to the PPL response.
  
  
  RESULTS
  We used gas chromatography mass spectrometry to quantify the change in plasma concentration of 35 fatty acids and 11 sterols between fasting and 3.5 hours after the consumption of a high-fat meal (PPL challenge) among 40 participants from the GOLDN study. Correlations between sterols, fatty acids and clinical measures were calculated. Mixed linear regression was used to evaluate associations between lipidomic profiles and genomic markers including single nucleotide polymorphisms (SNPs) and methylation markers derived from the Affymetrix 6.0 array and the Illumina Methyl450 array, respectively. After the PPL challenge, fatty acids increased as well as sterols associated with cholesterol absorption, while sterols associated with cholesterol synthesis decreased. PPL saturated fatty acids strongly correlated with triglycerides, very low-density lipoprotein, and chylomicrons. Two SNPs (rs12247017 and rs12240292) in the sorbin and SH3 domain containing 1 (SORBS1) gene were associated with b-Sitosterol after correction for multiple testing (P≤4.5*10(-10)). SORBS1 has been linked to obesity and insulin signaling. No other markers reached the genome-wide significance threshold, yet several other biologically relevant loci are highlighted (eg, PRIC285, a co-activator of PPARa).
  
  
  CONCLUSIONS
  Integration of lipidomic and genomic data has the potential to identify new biomarkers of CVD risk.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Irvin
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Degui
authors.initials: D
authors.lastname: Zhi
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Stella
authors.initials: S
authors.lastname: Aslibekyan
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Claas
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States of America.
authors.forename: Devin M
authors.initials: DM
authors.lastname: Absher
authors.affiliation: Department of Epidemiology, Atherothrombosis and Imaging, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; Instituto Madrileño de Estudios Avanzados Alimentacion, Madrid, Spain; Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, United States of America.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
authors.affiliation: Metabolon, Lipomics Division, Research Triangle Park, North Carolina, United States of America.
authors.forename: Steve
authors.initials: S
authors.lastname: Watkins
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics / Q000628:therapy; D002784:Cholesterol / Q000097:blood*; D030541:Databases, Genetic; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D008840:Microfilament Proteins; C432967:SORBS1 protein, human; D015534:Trans-Activators; D002784:Cholesterol