An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • University of Texas Health Science Center at Houston
  • University of Alabama at Birmingham
  • Washington University St. Louis
  • University of Maryland, Baltimore
  • Tufts University
  • Instituto Madrilenõs de Estudios Avanzados Alimentación
  • Instituto de Salud Carlos III
  • University of Minnesota Twin Cities
  • University of Utah
  • University of Washington

Details

Original languageEnglish (US)
Pages (from-to)722-729
Number of pages8
JournalJournal of lipid research
Volume59
Issue number4
StatusPublished - Jan 1 2018
Peer-reviewedYes

Abstract

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial AUI response to FFB (P = 1.88E-06), respectively. We sought to replicate the association for SIPA1L2 in the Heredity and Phenotype Intervention (HAPI) Heart Study, which included a high-fat meal challenge but not FFB treatment. The associated rare variants in GOLDN were not observed in the HAPI Heart study, and thus the gene-based result was not replicated. For functional validation, we found that gene transcript level of SIPA1L2 is associated with triglyceride postprandial AUI (P < 0.05) in GOLDN. Our study suggests unique genetic mechanisms contributing to the lipid response to the high-fat meal challenge and FFB therapy.—Geng, X., M. R. Irvin, B. Hidalgo, S. Aslibekyan, V. Srinivasasainagendra, P. An, A. C. Frazier-Wood, H. K. Tiwari, T. Dave, K. Ryan, J. M. Ordovas, R. J. Straka, M. F. Feitosa, P. N. Hopkins, I. Borecki, M. A. Province, B. D. Mitchell, D. K. Arnett, and D. Zhi. An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort.

Citation formats

APA

Geng, X., Irvin, M. R., Hidalgo, B., Aslibekyan, S., Srinivasasainagendra, V., An, P., ... Zhi, D. (2018). An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort. Journal of lipid research, 59(4), 722-729. https://doi.org/10.1194/jlr.P080333

Harvard

Geng, X, Irvin, MR, Hidalgo, B, Aslibekyan, S, Srinivasasainagendra, V, An, P, Frazier-Wood, AC, Tiwari, HK, Dave, T, Ryan, K, Ordovas, JM, Straka, RJ, Feitosa, MF, Hopkins, PN, Borecki, I, Province, MA, Mitchell, BD, Arnett, DK & Zhi, D 2018, 'An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort', Journal of lipid research, vol. 59, no. 4, pp. 722-729. https://doi.org/10.1194/jlr.P080333