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Report for Clinical Trial NCT01185587

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Sodium Channel Splicing in Heart Failure Trial

The purpose of this research is to see if investigators can detect truncated mRNA splice variants of the cardiac voltage-gated sodium (Na+) channel gene, SCN5A, in patients with a weak heart (Heart Failure) with or without an implantable cardioverter-defibrillator (ICD) and compare them to patients with a normal heart. Hypothesis: 1. Patients with reduced left ventricular ejection fraction have increased abundances truncated mRNA splice variants of the SCN5A gene, which portends to sodium channel dysfunction and an increased risk for sudden cardiac death. 2. Patients with implantable cardioverter-defibrillator devices (ICDs) who have experienced shock therapy have increased abundances of truncated mRNA splice variants of the SCN5A gene compared to similar congestive heart failure patients who have not experienced shock therapy.

NCT01185587 Atrial Fibrillation Atrial Flutter Heart Failure
MeSH: Heart Failure Atrial Fibrillation Atrial Flutter
HPO: Atrial fibrillation Atrial flutter Congestive heart failure Left ventricular dysfunction Paroxysmal atrial fibrillation Right ventricular failure


Primary Outcomes

Description: We will correlate the amount of white cell Na+ channel splice variants with ejection fraction in patients with an without heart failure and with the number of shocks in the patients with ICDs.

Measure: Amount of sodium channel splice variants

Time: At enrollment

Secondary Outcomes

Description: upstream signals for abnormal SCN5A mRNA splicing

Measure: ACE mRNA

Time: At enrollment

Description: upstream signals for abnormal SCN5A mRNA splicing

Measure: Ang II mRNA

Time: At enrollment

Description: upstream signals for abnormal SCN5A mRNA splicing

Measure: HIF-1α mRNA

Time: At enrollment

Time Perspective: Retrospective

Cohort


There are 4 SNPs

SNPs


1 E161K

A different SCN5A gene abnormality, the E161K mutation, has been shown to lead to decreased sodium current density and a an 11.9 mV positive shift in the cell membrane half-maximal activation potential.11 --- E161K ---


2 E28A

Relative levels of the full length mRNA isoform, E28A, were decreased by 24.7% in patients with CHF compared to control. --- E28A ---

Previously, we showed that the least sensitive measure was a reduction in E28A abundance by 24%. --- E28A ---


3 E28C

These three splicing variants for the nonfunctional sodium channel gene product were denoted E28B, E28C, and E28D. --- E28C ---

At the same time, the E28C and E28D mRNA abundances were increased 14.2 fold and 3.8 fold respectively in CHF patients compared to controls. --- E28C ---


4 E28D

These three splicing variants for the nonfunctional sodium channel gene product were denoted E28B, E28C, and E28D. --- E28C --- --- E28D ---

At the same time, the E28C and E28D mRNA abundances were increased 14.2 fold and 3.8 fold respectively in CHF patients compared to controls. --- E28C --- --- E28D ---



HPO Nodes


HPO:
Atrial fibrillation
Genes 62
CACNA1C KCNE2 MFAP5 CACNA2D1 TNNI3K FLNC GJA5 NPPA CACNB2 MYH7 MYL4 KCNA5 ANK2 NUP155 LMNA SLC25A4 HCN4 DTNA KCNH2 KCNJ2 FOS KCNJ5 RRM2B POLG SCN1B TLL1 SCN2B MYPN SCN4B AGPAT2 SCN5A MYOZ2 GATAD1 KCNQ1 NKX2-5 ABCC9 TWNK CASQ2 TAB2 XK CAVIN1 BSCL2 TMEM43 GATA5 ACTN2 CAV1 PPARG PRKAG2 TNNC1 DMPK POLG2 TNNI3 SGO1 TNNT2 PLN NEXN TRDN TTN CSRP3 RYR2 SMAD3 TBX5
Atrial flutter
Genes 13
DMPK LMNA ACADL GATA4 SGO1 GATA6 CLIC2 CRELD1 TNNI3K NR2F2 SCN3B SCN5A NUP155
Congestive heart failure
Genes 180
HJV TPM1 VHL HFE MYD88 ATP6V1A CACNA1S NDUFB11 FLNA SCO2 TCF4 FLNC MYH6 PNPLA2 MYH7 FBLN5 EYA4 MYL3 PSEN1 PSEN2 RASA1 CLIP2 DSP GPR35 DNAJC19 COG7 SGCD DTNA ENPP1 ACAD9 FOS HLA-DRB1 MAX GNPTAB KIF1B EFEMP2 NDUFAF3 BAG3 AGPAT2 WRN TUBB SLC19A2 PSMB8 IKBKG GBA AGGF1 ACTC1 BAZ1B PEX7 CDH23 CP CASR IRF5 RPS19 TSC1 TSC2 TMEM43 SLC25A26 CAV1 FXN RET PPARG ACVRL1 RFC2 IDS MDH2 PTEN GTF2IRD1 NSMCE2 GDF2 TMEM127 SELENON TTN HNRNPA1 NDUFB8 TF MECP2 TRIP4 HNRNPA2B1 ADCY5 ABCC6 ELAC2 RBM20 NDUFS2 STAT1 RYR1 EPG5 SNAP29 SLC25A3 MST1 SLC2A10 SLC17A5 IFIH1 GJA1 DES FGF23 TNNI3K JUP LIMK1 PHYH LDB3 FBN1 GTF2I GLA NDUFAF1 TRNC GLB1 LMNA COX1 ALMS1 COX2 COX3 SDHAF2 CYTB CLIC2 ATXN7 KCNJ5 SURF1 RAB3GAP2 ND1 MYPN TMEM70 SLC22A5 SCN4A ND4 PPA2 ND5 ND6 FGD1 PRKAR1A GATAD1 TRNE TRNF GNA11 CCN2 CCR6 CAVIN1 BSCL2 TRNH FGFR3 ELN HADHA TRNK TRNL1 HADHB HAMP DMD TRNQ PRKAG2 TRNS1 FH HBA1 TRNS2 GTPBP3 HBA2 TRNV TNNI3 TRNW TNNT2 ENG MAPRE2 PLN PLOD1 PRDM16 TRIM37 TBL2 ATP5F1A SDHA TAZ SDHB VCL ADAMTSL2 SDHC VCP SDHD CEP19 SMAD4 COL1A1 COL1A2 TPI1
Left ventricular dysfunction
Genes 62
POMT2 TGFB2 TGFB3 TGFBR1 LDLRAP1 TGFBR2 SDHAF1 MFAP5 MYH7 LDB3 MYH11 EYA4 FBN1 MYLK TRNC LMNA COX1 COX2 COX3 SLC25A4 CYTB FKRP SGCG LOX MAT2A RRM2B POLG ND1 ACTA2 ND5 ND6 LAMA2 TWNK CASQ2 TRNF APOB ELN TRNK TRNL1 PRKG1 POMT1 TRNQ TRNS1 TRNS2 POLG2 TRNV TRNW PPCS PRDM16 TRDN TTN LDLR ABCG5 ABCG8 TOP3A SDHA RYR2 SDHB SMAD3 SDHD PCSK9 FOXE3
Paroxysmal atrial fibrillation
Genes 12
CSRP3 KCNJ5 SCN1B SCN2B KCNE2 MYL4 SCN5A ABCC9 KCNA5 PRKAG2 TBX5 KCNJ2
Right ventricular failure
Genes 7
DAXX MYH7 ATRX BMPR2 SELENON SDHD TTN