Back to Search Start Over

Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis

Authors :
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 Srinivasan
Ify 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
Source :
Frontiers in Physiology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

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.

Details

Language :
English
ISSN :
1664042X
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Physiology
Publication Type :
Academic Journal
Accession number :
edsdoj.2d9a829ec51d4ab68f973ca04cd313fa
Document Type :
article
Full Text :
https://doi.org/10.3389/fphys.2022.909870