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Report for Clinical Trial NCT01185587
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
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.
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 70
SCN4B ANK2 RYR2 LMNA PRKAG2 MYPN SCN5A TNNT2 TNNI3K TNNI3 AGPAT2 CACNA2D1 HCN4 TTN POLG2 KCNE2 KCNQ1 SGO1 FOS MYOZ2 MYH7 LMNA CAVIN1 SCN2B PLN TNNC1 MFAP5 PRKAG2 TRDN TLL1 POLG CAV1 TAB2 TMEM43 ABCC9 SLC25A4 NKX2-5 ACTN2 XK TWNK KCNJ2 DTNA RRM2B KCNJ5 CACNB2 GJA5 FLNC TBX5 SCN5A BSCL2 CSRP3 KCNA5 CACNA1C MYL4 NEXN GATAD1 DMPK KCNQ1 NPPA PPARG KCNJ2 CAVIN1 GATA5 KCNQ1 SMAD3 CASQ2 KCNH2 NUP155 SCN1B SMAD3 hr>Atrial flutter
Genes 16
SGO1 LMNA ACADL CLIC2 DMPK LMNA GATA4 SCN5A TNNI3K SCN3B CLIC2 GATA6 CRELD1 NUP155 SCN5A NR2F2 hr>Congestive heart failure
Genes 250
PTEN HJV BAZ1B PEX7 HBA1 ND1 TNNT2 TRIM37 ACAD9 AGPAT2 TRNS1 LMNA EYA4 ND4 MYH7 LMNA RFC2 DSP NDUFAF3 TMEM43 SF3B1 HADHB SLC25A11 COX2 ENG HBA2 CEP19 LMNA TRNQ TRNQ GTF2IRD1 IDS MYL3 MYH7 ATXN7 ND6 HNRNPA1 CACNA1S FLNC XYLT2 EPG5 BSCL2 MYH6 FBN1 TRNK GBA SLC2A10 TRNV COX3 RET PRKAR1A MDH2 TRNK IRF5 MYH7 GPR35 TRNL1 ENG SURF1 STAT1 NSMCE2 SGCD ATP5F1A PLN TUBB PLOD1 CAV3 SLC25A26 SLC19A2 MYD88 GLA TPM1 GNPTAB RBM20 LMNA CDH23 TRNW CLIP2 MYPN TSC1 BMP2 HAMP TRNF ADCY5 LMNA LDB3 TTN ELN ENPP1 CAVIN1 TF MAX ELAC2 NDUFS2 CYTB DES DMD MYLK2 MAX TBL2 HLA-DRB1 ALMS1 PNPLA2 SLC17A5 COG7 SLC22A5 MYH7 PSMB8 SCN1B EYA4 MST1 FH TMEM127 MYH7 ND6 PPARG SDHA MAPRE2 COX1 JUP PSEN2 RASA1 ND5 SLC25A3 LMNA DLST TRNF IFIH1 ADCY5 SDHB SCN4A FXN GDF2 GTF2I HADHA GJA1 GNA11 RYR1 HFE SNAP29 TRNH TNNI3K FLNA TRNS2 SDHAF2 LMNA ACVRL1 TSC2 CASR FOS FGFR3 TRNK TRNL1 BCHE CCR6 CAV1 FGF23 VHL TMEM70 ADAMTSL2 DTNA PRKAG2 BAG3 TRNE SMAD4 TRNS2 ACAD9 SDHC PRKAR1A TAZ CAV1 ALMS1 TRNS1 NDUFB8 LIMK1 CLIC2 GATAD1 SDHD NDUFAF1 PRDM16 SELENON TRPM4 ACTC1 PRKAR1A SCN5A RPS19 TRIP4 FBLN5 SDHB NDUFB11 ATP6V1A HNRNPA2B1 CCN2 PSMB8 PPA2 TRNL1 COX1 RAB3GAP2 TNNI3 HFE COL1A2 TRNC CLIC2 DSP ND1 SCO2 JUP SDHD TRNW COX3 EFEMP2 AGGF1 TMEM127 TCF4 LMNA DSP KIF1B COL1A1 COX2 TPI1 GNPTAB FGD1 PSEN1 RET GLB1 KCNJ5 PHYH DES GTPBP3 HADHB WRN ND5 MECP2 HADHA GDNF VCL GLA TTN KIF1B VHL VCP ABCC6 PPARG CP XYLT1 TET2 DNAJC19 IKBKG NKX2-5 ABCC6 hr>Left ventricular dysfunction
Genes 67
TRNL1 SDHAF1 LDLRAP1 LDLR FBN1 RYR2 APOB POMT1 MAT2A FKRP LMNA TOP3A TRNW ABCG8 TRNC ND1 TRNS2 MYH7 LDB3 TRNS1 TTN POLG2 EYA4 POMT2 FOXE3 SMAD4 TGFBR2 SGCG PPCS DYSF TRNK CYTB TRDN SMAD3 MYH11 POLG ACTA2 COX2 SLC25A4 SDHD TGFB3 PRKG1 MYLK TWNK TRNQ SDHB POMT2 LAMA2 RRM2B ND6 MYH11 TGFB2 ND5 ELN COX1 MFAP5 PRDM16 TRNV SDHA COX3 MYH11 TRNF LOX PCSK9 CASQ2 TGFBR1 ABCG5 hr>Paroxysmal atrial fibrillation
Genes 12
KCNJ5 SCN5A CSRP3 KCNA5 KCNJ2 SCN2B MYL4 ABCC9 TBX5 KCNE2 SCN1B PRKAG2 hr>Right ventricular failure
Genes 7
DAXX SDHD TTN BMPR2 MYH7 SELENON ATRX hr>