Genomics of Post-prandial Lipidomic Phenotypes in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jun 7

PMID 24905834

Citations 20

Authors

Marguerite R Irvin

Degui Zhi

Stella Aslibekyan

Steven A Claas

Devin M Absher

Jose M Ordovas

Hemant K Tiwari

Steve Watkins

Donna K Arnett

Affiliations

Soon will be listed here.

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.

Methods And 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.

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References

Pihlajamaki J, Gylling H, Miettinen T, Laakso M . Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. J Lipid Res. 2003; 45(3):507-12. DOI: 10.1194/jlr.M300368-JLR200. View

Wang K, Li M, Hakonarson H . ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010; 38(16):e164. PMC: 2938201. DOI: 10.1093/nar/gkq603. View

Neurauter A, Bonyhadi M, Lien E, Nokleby L, Ruud E, Camacho S . Cell isolation and expansion using Dynabeads. Adv Biochem Eng Biotechnol. 2007; 106:41-73. DOI: 10.1007/10_2007_072. View

Surapureddi S, Yu S, Bu H, Hashimoto T, Yeldandi A, Kashireddy P . Identification of a transcriptionally active peroxisome proliferator-activated receptor alpha -interacting cofactor complex in rat liver and characterization of PRIC285 as a coactivator. Proc Natl Acad Sci U S A. 2002; 99(18):11836-41. PMC: 129355. DOI: 10.1073/pnas.182426699. View

Matthan N, Zhu L, Pencina M, DAgostino R, Schaefer E, Lichtenstein A . Sex-specific differences in the predictive value of cholesterol homeostasis markers and 10-year cardiovascular disease event rate in Framingham Offspring Study participants. J Am Heart Assoc. 2013; 2(1):e005066. PMC: 3603247. DOI: 10.1161/JAHA.112.005066. View

Bouwens M, Afman L, Muller M . Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid beta-oxidation: functional role of peroxisome proliferator activated receptor alpha in human peripheral blood mononuclear cells. Am J Clin Nutr. 2007; 86(5):1515-23. DOI: 10.1093/ajcn/86.5.1515. View

OConnor B, Eun S, Ye Z, Zozulya A, Lich J, Moore C . Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses. Proc Natl Acad Sci U S A. 2008; 105(35):13015-20. PMC: 2529027. DOI: 10.1073/pnas.0803386105. View

Micha R, Mozaffarian D . Saturated fat and cardiometabolic risk factors, coronary heart disease, stroke, and diabetes: a fresh look at the evidence. Lipids. 2010; 45(10):893-905. PMC: 2950931. DOI: 10.1007/s11745-010-3393-4. View

Gylling H, Hallikainen M, Rajaratnam R, Simonen P, Pihlajamaki J, Laakso M . The metabolism of plant sterols is disturbed in postmenopausal women with coronary artery disease. Metabolism. 2009; 58(3):401-7. DOI: 10.1016/j.metabol.2008.10.015. View

10.

Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S . Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2006; 115(4):450-8. DOI: 10.1161/CIRCULATIONAHA.106.637793. View

11.

Pevsner J . Analysis of genomic DNA with the UCSC genome browser. Methods Mol Biol. 2009; 537:277-301. DOI: 10.1007/978-1-59745-251-9_14. View

12.

Kent W, Hsu F, Karolchik D, Kuhn R, Clawson H, Trumbower H . Exploring relationships and mining data with the UCSC Gene Sorter. Genome Res. 2005; 15(5):737-41. PMC: 1088302. DOI: 10.1101/gr.3694705. View

13.

Matthan N, Pencina M, LaRocque J, Jacques P, DAgostino R, Schaefer E . Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD. J Lipid Res. 2009; 50(9):1927-35. PMC: 2724787. DOI: 10.1194/jlr.P900039-JLR200. View

14.

Kikutani H, Kumanogoh A . Semaphorins in interactions between T cells and antigen-presenting cells. Nat Rev Immunol. 2003; 3(2):159-67. DOI: 10.1038/nri1003. View

15.

Bevan S, Traylor M, Adib-Samii P, Malik R, Paul N, Jackson C . Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations. Stroke. 2012; 43(12):3161-7. DOI: 10.1161/STROKEAHA.112.665760. View

16.

Nordestgaard B, Benn M, Schnohr P, Tybjaerg-Hansen A . Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007; 298(3):299-308. DOI: 10.1001/jama.298.3.299. View

17.

Liang Y, Tedder T . Identification of a CD20-, FcepsilonRIbeta-, and HTm4-related gene family: sixteen new MS4A family members expressed in human and mouse. Genomics. 2001; 72(2):119-27. DOI: 10.1006/geno.2000.6472. View

18.

Cuchel M, Schaefer E, Millar J, Jones P, Dolnikowski G, Vergani C . Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males. Arterioscler Thromb Vasc Biol. 1997; 17(10):1910-7. DOI: 10.1161/01.atv.17.10.1910. View

19.

Miettinen T, Tilvis R, Kesaniemi Y . Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol. 1990; 131(1):20-31. DOI: 10.1093/oxfordjournals.aje.a115479. View

20.

Smith J, Melander O, Sjogren M, Hedblad B, Engstrom G, Newton-Cheh C . Genetic polymorphisms confer risk of atrial fibrillation in patients with heart failure: a population-based study. Eur J Heart Fail. 2012; 15(3):250-7. PMC: 3576900. DOI: 10.1093/eurjhf/hfs176. View