TY - JOUR
T1 - Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease
T2 - an individual level meta-analysis
AU - Schillemans, Tessa
AU - Tragante, Vinicius
AU - Maitusong, Buamina
AU - Gigante, Bruna
AU - Cresci, Sharon
AU - Laguzzi, Federica
AU - Vikström, Max
AU - Richards, Mark
AU - Pilbrow, Anna
AU - Cameron, Vicky
AU - Foco, Luisa
AU - Doughty, Robert N.
AU - Kuukasjärvi, Pekka
AU - Allayee, Hooman
AU - Hartiala, Jaana A.
AU - Tang, W. H.Wilson
AU - Lyytikäinen, Leo Pekka
AU - Nikus, Kjell
AU - Laurikka, Jari O.
AU - Srinivasan, Sundararajan
AU - Mordi, Ify R.
AU - Trompet, Stella
AU - Kraaijeveld, Adriaan
AU - van Setten, Jessica
AU - Gijsberts, Crystel M.
AU - Maitland-van der Zee, Anke H.
AU - Saely, Christoph H.
AU - Gong, Yan
AU - Johnson, Julie A.
AU - Cooper-DeHoff, Rhonda M.
AU - Pepine, Carl J.
AU - Casu, Gavino
AU - Leiherer, Andreas
AU - Drexel, Heinz
AU - Horne, Benjamin D.
AU - van der Laan, Sander W.
AU - Marziliano, Nicola
AU - Hazen, Stanley L.
AU - Sinisalo, Juha
AU - Kähönen, Mika
AU - Lehtimäki, Terho
AU - Lang, Chim C.
AU - Burkhardt, Ralph
AU - Scholz, Markus
AU - Jukema, J. Wouter
AU - Eriksson, Niclas
AU - Åkerblom, Axel
AU - James, Stefan
AU - Held, Claes
AU - Hagström, Emil
AU - Spertus, John A.
AU - Algra, Ale
AU - de Faire, Ulf
AU - Åkesson, Agneta
AU - Asselbergs, Folkert W.
AU - Patel, Riyaz S.
AU - Leander, Karin
N1 - Funding Information:
Dr Patel is funded by a British Heart Foundation Intermediate Fellowship (FS/14/76/30933). Dr. Cresci is supported, in part, by the National Institutes of Health (Cresci R01 NR013396); Dr. Sander W. van der Laan is funded through EU H2020 TO_AITION (grant number: 848146). Dr Pilbrow is funded by the Health Research Council of New Zealand and the Christchurch Heart Institute Trust; Prof. Dr. J. W. Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032); T. Schillemans is supported by the Swedish Research Council no 2017-00822.
PY - 2022/6/23
Y1 - 2022/6/23
N2 - 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.
AB - 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.
KW - Coronary heart disease
KW - Polymorphisms
KW - PPARGC1A
KW - Meta-analysis
KW - SNP
KW - cohort studies
KW - meta-analysis
KW - SNPs
KW - coronary heart disease
KW - polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=85133851698&partnerID=8YFLogxK
U2 - 10.3389/fphys.2022.909870
DO - 10.3389/fphys.2022.909870
M3 - Article
C2 - 35812313
AN - SCOPUS:85133851698
SN - 1664-042X
VL - 13
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 909870
ER -