Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: an individual level meta-analysis

Tessa Schillemans, Vinicius Tragante, Buamina Maitusong, Bruna Gigante, Sharon Cresci, Federica Laguzzi, Max Vikström, Mark Richards, Anna Pilbrow, Vicky Cameron, Luisa Foco, Robert N. Doughty, Pekka Kuukasjärvi, Hooman Allayee, Jaana A. Hartiala, W. H.Wilson Tang, Leo Pekka Lyytikäinen, Kjell Nikus, Jari O. Laurikka, Sundararajan SrinivasanIfy R. Mordi, Stella Trompet, Adriaan Kraaijeveld, Jessica van Setten, Crystel M. Gijsberts, Anke H. Maitland-van der Zee, Christoph H. Saely, Yan Gong, Julie A. Johnson, Rhonda M. Cooper-DeHoff, Carl J. Pepine, Gavino Casu, Andreas Leiherer, Heinz Drexel, Benjamin D. Horne, Sander W. van der Laan, Nicola Marziliano, Stanley L. Hazen, Juha Sinisalo, Mika Kähönen, Terho Lehtimäki, Chim C. Lang, Ralph Burkhardt, Markus Scholz, J. Wouter Jukema, Niclas Eriksson, Axel Åkerblom, Stefan James, Claes Held, Emil Hagström, John A. Spertus, Ale Algra, Ulf de Faire, Agneta Åkesson, Folkert W. Asselbergs, Riyaz S. Patel, Karin Leander (Lead / Corresponding author)

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Abstract

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98–1.05 and rs7672915, HR: 0.97, 95% CI 0.94–1.00; rs3755863, HR: 1.02, 95% CI 0.99–1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.

Original languageEnglish
Article number909870
Number of pages14
JournalFrontiers in Physiology
Volume13
DOIs
Publication statusPublished - 23 Jun 2022

Keywords

  • Coronary heart disease
  • Polymorphisms
  • PPARGC1A
  • Meta-analysis
  • SNP
  • cohort studies
  • meta-analysis
  • SNPs
  • coronary heart disease
  • polymorphisms

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