PMID- 31422771
OWN - NLM
STAT- MEDLINE
DCOM- 20200504
LR  - 20240117
IS  - 1532-429X (Electronic)
IS  - 1097-6647 (Print)
IS  - 1097-6647 (Linking)
VI  - 21
IP  - 1
DP  - 2019 Aug 19
TI  - Genetic variants of HIF1alpha are associated with right ventricular fibrotic load in 
      repaired tetralogy of Fallot patients: a cardiovascular magnetic resonance study.
PG  - 51
LID - 10.1186/s12968-019-0555-2 [doi]
LID - 51
AB  - BACKGROUND: Studies suggest that right ventricular (RV) fibrosis is associated 
      with RV remodeling and long-term outcomes in patients with tetralogy of Fallot 
      (TOF). Pre-operative hypoxia may increase expression of hypoxia inducible 
      factor-1-alpha (HIF1alpha) and promote transforming growth factor beta1 (TGFbeta1)-mediated 
      fibrosis. We hypothesized that there would be associations between: (1) RV 
      fibrosis and RV function, (2) HIF1alpha variants and RV fibrosis, and (3) HIF1alpha 
      variants and RV function among post-surgical TOF cases. METHODS: We 
      retrospectively measured post-surgical fibrotic load (indexed volume and fibrotic 
      score) from 237 TOF cases who had existing cardiovascular magnetic resonance 
      imaging using late gadolinium enhancement (LGE), and indicators of RV remodeling 
      (i.e., ejection fraction [RVEF] and end-diastolic volume indexed [RVEDVI]). 
      Genetic data were available in 125 cases. Analyses were conducted using 
      multivariable linear mixed-effects regression with a random intercept and 
      multivariable generalized Poisson regression with a random intercept. RESULTS: 
      Indexed fibrotic volume and fibrotic score significantly decreased RVEF by 1.6% 
      (p = 0.04) and 0.9% (p = 0.03), respectively. Indexed fibrotic volume and score 
      were not associated with RVEDVI. After adjusting for multiple comparisons, 6 of 
      the 48 HIF1alpha polymorphisms (representing two unique signals) were associated with 
      fibrotic score. None of the HIF1alpha polymorphisms were associated with indexed 
      fibrotic volume, RVEDVI, or RVEF. CONCLUSION: The association of some HIF1alpha 
      polymorphisms and fibrotic score suggests that HIF1alpha may modulate the fibrotic 
      response in TOF.
FAU - Hoang, Thanh T
AU  - Hoang TT
AD  - Department of Epidemiology, Human Genetics, and Environmental Sciences, UTHealth 
      School of Public Health, Houston, TX, USA.
FAU - Manso, Paulo Henrique
AU  - Manso PH
AD  - Department of Pediatrics, Ribeiro Preto Medical School USP, Ribeirao Preto, 
      Brazil.
FAU - Edman, Sharon
AU  - Edman S
AD  - Division of Cardiology, Children's Hospital of Philadelphia, Abramson Research 
      Center 702A, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
FAU - Mercer-Rosa, Laura
AU  - Mercer-Rosa L
AD  - Division of Cardiology, Children's Hospital of Philadelphia, Abramson Research 
      Center 702A, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
AD  - Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA, USA.
FAU - Mitchell, Laura E
AU  - Mitchell LE
AD  - Department of Epidemiology, Human Genetics, and Environmental Sciences, UTHealth 
      School of Public Health, Houston, TX, USA.
FAU - Sewda, Anshuman
AU  - Sewda A
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, NY, USA.
FAU - Swartz, Michael D
AU  - Swartz MD
AD  - Department of Biostatistics and Data Science, UTHealth School of Public Health, 
      Houston, TX, USA.
FAU - Fogel, Mark A
AU  - Fogel MA
AD  - Division of Cardiology, Children's Hospital of Philadelphia, Abramson Research 
      Center 702A, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
AD  - Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA, USA.
FAU - Agopian, A J
AU  - Agopian AJ
AD  - Department of Epidemiology, Human Genetics, and Environmental Sciences, UTHealth 
      School of Public Health, Houston, TX, USA.
FAU - Goldmuntz, Elizabeth
AU  - Goldmuntz E
AUID- ORCID: 0000-0003-2936-4396
AD  - Division of Cardiology, Children's Hospital of Philadelphia, Abramson Research 
      Center 702A, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA. 
      goldmuntz@email.chop.edu.
AD  - Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA, USA. goldmuntz@email.chop.edu.
LA  - eng
GR  - P50 HL074731/HL/NHLBI NIH HHS/United States
GR  - T32 HL007915/HL/NHLBI NIH HHS/United States
GR  - UL1TR000003/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190819
PL  - England
TA  - J Cardiovasc Magn Reson
JT  - Journal of cardiovascular magnetic resonance : official journal of the Society 
      for Cardiovascular Magnetic Resonance
JID - 9815616
RN  - 0 (Contrast Media)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - K2I13DR72L (Gadolinium DTPA)
SB  - IM
MH  - Cardiac Surgical Procedures
MH  - Contrast Media/administration & dosage
MH  - Female
MH  - Fibrosis
MH  - Gadolinium DTPA/administration & dosage
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics
MH  - Infant
MH  - Infant, Newborn
MH  - *Magnetic Resonance Imaging, Cine
MH  - Male
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Predictive Value of Tests
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Tetralogy of Fallot/*diagnostic imaging/genetics/physiopathology/surgery
MH  - Treatment Outcome
MH  - *Ventricular Function, Right
MH  - *Ventricular Remodeling
PMC - PMC6699069
OTO - NOTNLM
OT  - Cardiovascular magnetic resonance imaging
OT  - Fibrosis
OT  - HIF1alpha
OT  - Right ventricular ejection fraction
OT  - Right ventricular end-diastolic volume
OT  - Tetralogy of Fallot
COIS- The authors declare that they have no competing interests.
EDAT- 2019/08/20 06:00
MHDA- 2020/05/06 06:00
PMCR- 2019/08/19
CRDT- 2019/08/20 06:00
PHST- 2019/01/21 00:00 [received]
PHST- 2019/06/14 00:00 [accepted]
PHST- 2019/08/20 06:00 [entrez]
PHST- 2019/08/20 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2019/08/19 00:00 [pmc-release]
AID - S1097-6647(23)00224-7 [pii]
AID - 555 [pii]
AID - 10.1186/s12968-019-0555-2 [doi]
PST - epublish
SO  - J Cardiovasc Magn Reson. 2019 Aug 19;21(1):51. doi: 10.1186/s12968-019-0555-2.