title: The Number of GT(n) Repeats in the Hemeoxygenase-1 Gene Promoter is Increased in Pediatric Heart Failure but is Unrelated to Renal, Antioxidant and Anti-inflammatory Markers.
abstract: Products of hemeoxygenase (HO)-1 have anti-inflammatory and antioxidant functions. The HO-1 promoter has a variable number of GT(n) repeats: A low number (n < 23) is associated with high transcriptional activity in response to oxidative stress. We hypothesized that the frequency of GT(n) repeats in pediatric heart failure (HF) reflects plasma biomarkers of different disease processes: the soluble receptor for advance glycation end products (sRAGE, marking cellular activation), oxLDL (oxidative stress), NGAL (impaired renal function), HIF-1α (hypoxia) and hsCRP (inflammation). Sixty HF children [aged 4-14 years, 30 with HF due to idiopathic dilated cardiomyopathy (IDCM), 30 due to chronic renal failure (CRF)] were compared to 20 healthy controls (HC). Leukocyte HO-1 GT(n) repeats were determined by PCR, plasma markers by ELISA or nephelometry. The number of GT(n) repeats in the HF patients was higher than the number of repeats in the controls, with no difference between the patient groups (p < 0.001). sRAGE, oxLDL, HIF-1α, NGAL and hsCRP were higher in both HF groups compared to HC (all p < 0.01). IDCM had higher sRAGEs and HIF-1α compared to CRF patients (p < 0.01). NGAL was higher in CRF compared to IDCM (p < 0.01). None of the plasma/serum markers correlated with the number of GT(n) repeats in any group. The number of HO-1 promoter GT(n) polymorphism is increased in both IDCM and CRF children with HF, but is unrelated to plasma markers of different pathological processes. This casts doubts on the clinical value of the number of GT(n) repeats in pediatric HF.
authors.affiliation: Anesthesiology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Sherif
authors.initials: S
authors.lastname: Sayed
authors.forename: Naglaa K
authors.initials: NK
authors.lastname: Idriss
authors.forename: Andrew
authors.initials: A
authors.lastname: Blann
authors.forename: Hayam G
authors.initials: HG
authors.lastname: Sayyed
authors.forename: D M
authors.initials: DM
authors.lastname: Raafat
authors.forename: Doaa
authors.initials: D
authors.lastname: Fouad
authors.forename: M S K
authors.initials: MS
authors.lastname: Tawfeek
mesh_terms: D000293:Adolescent; D000975:Antioxidants / Q000378:metabolism; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000150:complications; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006333:Heart Failure / Q000209:etiology / Q000235:genetics*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D007249:Inflammation; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009391:Nephelometry and Turbidimetry / Q000379:methods; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D051547:Heme Oxygenase-1
references.citation: Mol Immunol. 2011 Sep;48(15-16):1793-9
references.pmid: 21640381
references.citation: Circulation. 2009 Apr 14;119(14):1977-2016
references.pmid: 19324967
references.citation: Clin Sci (Lond). 2013 Jul 1;125(2):99-108
references.pmid: 23406266
references.citation: Eur J Heart Fail. 2010 Oct;12(10):1092-100
references.pmid: 20685687
references.citation: Eur Rev Med Pharmacol Sci. 2013 Apr;17(7):903-11
references.pmid: 23640436
references.citation: Semin Nephrol. 2012 Jan;32(1):121-8
references.pmid: 22365170
references.citation: J Card Fail. 2010 Jan;16(1):49-54
references.pmid: 20123318
references.citation: Int J Cardiol. 2013 Apr 30;165(1):51-5
references.pmid: 21872946
references.citation: Arterioscler Thromb Vasc Biol. 2000 Oct;20(10):2243-7
references.pmid: 11031210
references.citation: J Am Coll Cardiol. 2008 Sep 16;52(12 ):971-8
references.pmid: 18786476
references.citation: BMC Med Genet. 2009 Apr 23;10 :36
references.pmid: 19389234
references.citation: Curr Opin Lipidol. 2006 Oct;17(5):502-9
references.pmid: 16960498
references.citation: Exp Clin Cardiol. 2013 Spring;18(2):107-9
references.pmid: 23940432
references.citation: Free Radic Res. 2011 Jul;45(7):810-9
references.pmid: 21545264
references.citation: Life Sci. 2012 Oct 29;91(17-18):828-36
references.pmid: 22917518
references.citation: Heart. 2004 Nov;90(11):1269-74
references.pmid: 15486118
references.citation: Cell Signal. 2012 Jun;24(6):1215-21
references.pmid: 22349240
references.citation: Curr Med Chem. 2009;16(8):940-52
references.pmid: 19275604
references.citation: Hum Genet. 2002 Jul;111(1):1-8
references.pmid: 12136229
references.citation: Diabetes Care. 2009 Jul;32(7):1218-20
references.pmid: 19366975
references.citation: J Biol Chem. 2012 Sep 28;287(40):33720-32
references.pmid: 22879597
references.citation: PLoS One. 2013 Sep 13;8(9):e74302
references.pmid: 24058542
references.citation: Cardiovasc Res. 2012 Apr 1;94(1):77-86
references.pmid: 22258630
references.citation: Int J Nephrol Renovasc Dis. 2013 Oct 02;6:181-6
references.pmid: 24124387
references.citation: Circulation. 2010 May 4;121(17 ):1912-25
references.pmid: 20404253
references.citation: Dis Model Mech. 2013 Jul;6(4):1012-20
references.pmid: 23592614
references.citation: Nephrol Dial Transplant. 2009 Jan;24(1):186-93
references.pmid: 18711222
references.citation: EMBO J. 2012 May 30;31(11):2448-60
references.pmid: 22562152
references.citation: Cardiovasc Diabetol. 2013 Aug 28;12:125
references.pmid: 23984879
references.citation: J Endovasc Ther. 2002 Aug;9(4):385-94
references.pmid: 12222997
references.citation: Cell Stress Chaperones. 2012 May;17 (3):329-38
references.pmid: 22120665
references.citation: Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5987-91
references.pmid: 8016102
references.citation: Am Heart J. 2012 Nov;164(5):742-749.e3
references.pmid: 23137505
references.citation: Acta Cardiol. 1998;53(5):253-60
references.pmid: 9922802
references.citation: J Chin Med Assoc. 2013 Jun;76(6):312-8
references.pmid: 23602216
references.citation: J Biomed Sci. 2010 Feb 23;17 :12
references.pmid: 20175935
references.citation: World J Cardiol. 2012 Nov 26;4(11):302-8
references.pmid: 23185651
references.citation: Arch Dis Child. 2007 Sep;92(9):812-6
references.pmid: 17715446
references.citation: Biomed Res Int. 2013;2013:947157
references.pmid: 23936859
references.citation: Heart Fail Clin. 2010 Oct;6(4):401-13, vii
references.pmid: 20869642
references.citation: Am J Physiol Renal Physiol. 2012 Apr 1;302(7):F791-800
references.pmid: 22205229
references.citation: Atherosclerosis. 2009 Oct;206(2):540-5
references.pmid: 19368923
references.citation: J Am Coll Cardiol. 2002 Mar 20;39(6):957-62
references.pmid: 11897436
references.citation: Eur J Clin Invest. 2005 Dec;35(12 ):731-7
references.pmid: 16313248
references.citation: Biomark Med. 2010 Apr;4(2):265-80
references.pmid: 20406069
references.citation: Appl Biochem Biotechnol. 2014 Apr;172(8):4062-77
references.pmid: 24610037
references.citation: Br J Biomed Sci. 2003;60(3):155-60
references.pmid: 14560792
references.citation: J Card Fail. 2008 Mar;14 (2):133-9
references.pmid: 18325460