SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00187733

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Influence of OCTN2 Variants on Carnitine Status and Plasma Triglycerides

The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. Previously, the investigators have recruited a cohort of healthy volunteers (Studies of Pharmacogenetics in Ethnically-Diverse Populations, or SOPHIE) and have resequenced the coding region of a number of membrane transporter genes to identify genetic polymorphisms in these genes. Subjects in this cohort have agreed to be called back for recruitment in further studies based on their own genetic sequence, allowing the investigators the possibility to prospectively study the influence of genetic polymorphisms on particular phenotypes (i.e., genotype-to-phenotype studies). The investigators plan to take a genotype-to-phenotype approach to study the influence of specific polymorphisms in the novel organic cation transporter 2 (OCTN2) gene on carnitine and lipid metabolism in healthy subjects.

NCT00187733 Carnitine Transporter Deficiency
MeSH: Muscular Diseases Cardiomyopathies Hyperammonemia
HPO: Cardiomyopathy Hyperammonemia Myopathy

1 Interventions

Name: Fasting blood and urine collection

Description: Not applicable no drugs dispensed

Type: Other

Fasting



Time Perspective: Prospective

Cohort


There are 5 SNPs

SNPs


1 F17L

We found eight amino acid sequence variants of OCTN2, of which three (Phe17Leu, Leu144Phe, and Pro549Ser) were polymorphic in at least one ethnic group. --- Phe17Leu ---

When assayed for functional activity by expression in human embryonic kidney 293 cells, using as probes both the endogenous substrate (l-carnitine) and the organic cation tetraethylammonium, three variants showed functional differences from the reference OCTN2 (Phe17Leu, Tyr449Asp, Val481Phe; p < 0.05). --- Phe17Leu ---

Further studies of the Phe17Leu polymorphism showed a reduced V(max) for l-carnitine transport to approximately 50% of the reference OCTN2. --- Phe17Leu ---

Confocal microscopy studies using an OCTN2-GFP fusion protein showed that Phe17Leu had distinct subcellular localization from the reference OCTN2, with diffuse cytoplasmic retention of Phe17Leu, in contrast to reference OCTN2, which localized specifically to the plasma membrane. --- Phe17Leu ---

Confocal microscopy studies using an OCTN2-GFP fusion protein showed that Phe17Leu had distinct subcellular localization from the reference OCTN2, with diffuse cytoplasmic retention of Phe17Leu, in contrast to reference OCTN2, which localized specifically to the plasma membrane. --- Phe17Leu --- --- Phe17Leu ---


2 L144F

We found eight amino acid sequence variants of OCTN2, of which three (Phe17Leu, Leu144Phe, and Pro549Ser) were polymorphic in at least one ethnic group. --- Phe17Leu --- --- Leu144Phe ---


3 P549S

We found eight amino acid sequence variants of OCTN2, of which three (Phe17Leu, Leu144Phe, and Pro549Ser) were polymorphic in at least one ethnic group. --- Phe17Leu --- --- Leu144Phe --- --- Pro549Ser ---


4 V481F

When assayed for functional activity by expression in human embryonic kidney 293 cells, using as probes both the endogenous substrate (l-carnitine) and the organic cation tetraethylammonium, three variants showed functional differences from the reference OCTN2 (Phe17Leu, Tyr449Asp, Val481Phe; p < 0.05). --- Phe17Leu --- --- Tyr449Asp --- --- Val481Phe ---


5 Y449D

When assayed for functional activity by expression in human embryonic kidney 293 cells, using as probes both the endogenous substrate (l-carnitine) and the organic cation tetraethylammonium, three variants showed functional differences from the reference OCTN2 (Phe17Leu, Tyr449Asp, Val481Phe; p < 0.05). --- Phe17Leu --- --- Tyr449Asp ---



HPO Nodes


HPO:
Cardiomyopathy
Genes 431
TPM1 TPM2 TPM3 CDKN1C TACO1 HFE H19-ICR SDHAF1 TREX1 ERBB3 ERCC2 EYA4 ERCC3 BRIP1 ERCC4 ACADL HLA-B ACADS PDGFRA ACADVL MICOS13 PDHA1 DNAJC19 ENPP1 SPEG SMC1A ACTA1 MC2R PEX1 ACTC1 PEX6 PEX7 DPM3 PEX10 PEX12 PEX13 PEX14 ANO5 HMGCL KLHL41 ACTN2 CHKB ADAR TTN HNRNPA1 TTPA TTR TRIP4 HNRNPA2B1 ADCY5 WARS2 ELAC2 PGM1 RYR1 RYR2 RNU4ATAC FANCA FANCC FANCD2 FANCE SLC25A3 SLC2A10 FAH FANCB FANCF FANCG PHYH AARS2 FKTN CLN3 AGL RAB3GAP2 RNASEH2C HPS1 SCN5A MIPEP MIB1 COA5 AHCY GPC4 PEX16 HRAS SCO1 GTF2H5 PKP2 MMP1 MAD2L2 MTO1 FTO PRKAG2 FHL1 FHL2 POMK GMPPB PLN LTBP4 SLC30A10 D2HGDH SDHA SDHB VCL VCP SDHD PMM2 HJV POMT2 TMEM126A NDUFB11 COL7A1 FLNC FOXRED1 MYOT NDUFAF5 ANK1 NEBL TAPT1 SLC25A4 CLIP2 CISD2 RNASEH2A FKRP SGCA WFS1 SGCB SGCD ACAD9 SGSH FOS RRM2B POLG GNPTAB PEX3 NDUFAF3 BAG3 AGPAT2 COX6B1 DOLK SLC19A2 KCNAB2 COX7B COX8A COX10 POMGNT1 COX15 TWNK XK SAMHD1 FASTKD2 TMEM43 GATA5 POMT1 IDH2 TXNRD2 FXN PPARG XRCC2 CPT1A XRCC4 CPT2 FANCM GTF2IRD1 IDUA SKI TCAP SLC40A1 COA8 ABCC6 RBM20 PEX26 RBCK1 NDUFA11 SLC4A1 EPG5 PPP1CB MTFMT LIMS2 CRYAB NBAS LIPT1 VAC14 PIGT NDUFAF4 IGF2 ACAD8 ARSB ATP6 COX1 COX2 UBE2T COX3 KLF1 NEK8 FLAD1 ANKRD1 ND1 ND2 SLC22A5 ND3 ND4 NAXD MRPS14 PPA2 ND5 ND6 ANKRD11 MPLKIP GATAD1 AGK KBTBD13 TRNE TRNF NDUFAF6 CAVIN1 TRNH TRNK TRNL1 HAMP RERE TRNN TRNQ TRNS1 TRNS2 RNASEH1 TRNT TRNV TRNW SUFU MAP2K1 MAP2K2 PRDM16 NEXN SLX4 MMUT H19 MGME1 ATPAF2 SOS1 MYBPC3 ATP5F1D ATP5F1E GABRD COX20 UBR1 IL12B ATP6V1A MYH6 MYH7 ANKS6 NDUFS7 MYL2 MYL3 DCAF8 PSEN1 PSEN2 PET100 SPTA1 SPTB TMEM126B MRPL44 RNF113A VPS33A NAGA NAGLU MAP3K20 GATA4 MYOZ2 BBS2 GBE1 CDH23 NDUFA2 NDUFA4 PEX11B GPR101 ITGA7 NEB NDUFA9 NDUFA10 COQ2 BCS1L NDUFB8 NDUFS1 NDUFS2 MRPS22 NDUFS3 STAR NDUFV1 NDUFS4 ITPA NDUFS8 NDUFV2 FBXL4 IFIH1 DES GJA5 JUP COA6 PTPN11 NEU1 NF1 GLA GPC3 NDUFA12 BRCA1 GLB1 ALMS1 BRAF BRCA2 CLPB FIG4 KCNH1 SURF1 KCNJ8 MYPN TMEM70 SYNE2 VPS13A PEX19 C1QBP PEX2 PEX5 KCNQ1 DLD DMD SARDH MYO18B RMND1 GTPBP3 KCNQ1OT1 GNS ALG1 TAZ RAD51 RAD51C RNASEH2B KRAS RAF1 LIAS SCO2 NPPA PNPLA2 SLC25A20 NRAS DSC2 MLX NUP107 GNE DSG2 NDUFAF2 DSP COG7 DTNA SYNE1 TAF1A HGSNAT SLC19A3 LAMA2 LAMA3 LAMA4 JPH2 BAZ1B LAMB3 ABCC9 LAMC2 LAMP2 FANCL AIP CAV1 RFC2 ECHS1 PPCS SHOC2 SELENON BOLA3 OPA1 CSRP3 PALB2 TSFM GSN RFWD3 MLYCD YARS2 TFR2 RIT1 TGFB1 TGFB3 NDUFA13 RMRP USP8 TNNI3K LIMK1 GTF2E2 LDB3 TRNT1 GTF2I ABHD5 NDUFAF1 LMNA ATAD3A TK2 COQ4 GUSB FANCI GYG1 GYS1 MRAP TMPO BSCL2 HSD17B10 ELN HADHA MRPL3 HADHB HADH EMD TANGO2 TNNC1 POLG2 TNNI3 KAT6B HBB TNNT2 PCCA PCCB NNT HCCS HACD1 TBL2 TOP3A EPB42 COX14 TPI1
Hyperammonemia
Genes 45
GLUL ATP5F1D CYC1 MMAA HLCS DLD NBAS OTC SERAC1 HMGCL SLC25A20 CAD HADHA MCCC2 HADHB HADH UQCRC2 MCCC1 NDUFA6 TANGO2 CPS1 CPT1A SLC7A7 CPT2 ACADL MMAB ACAT1 PCCA PCCB BTD ACAD9 MMUT ASL NR1H4 NAGS TUFM SLC25A13 SLC25A15 TMEM70 SLC22A5 GLUD1 CA5A ASS1 ATPAF2 ARG1
Myopathy
Genes 288
TPM1 TPM2 TPM3 GABRD SDHAF1 MYF6 MYH2 MYH6 MYH7 ZBTB20 MYL2 ACACA PSEN1 PSEN2 ACADL ACADS CENPF MYO9A CCDC174 CFL2 INPP5K ACTA1 GAS1 MAP3K20 SLC5A7 ACTC1 CDH23 CHAT ANO5 AK9 KLHL41 ACTN2 ITGA7 NEB PTCH1 CHKB PTEN DYSF COLQ NDUFB3 PGAM2 TTN HNRNPA1 TRIP4 HNRNPA2B1 CHRNA1 PGK1 GFER NDUFS2 GFPT1 CHRNB1 RYR1 CHRND CHRNE B4GALT1 SLC25A3 STIM1 NEFH DES UBA1 GK KLHL9 PANK2 GCLC FKTN GLI2 AGL ALG14 MYPN SYNE2 SCN4A SCN5A VAMP1 VPS13A C1QBP MYMK AP1S2 FGF8 PYGM AKT1 FGFR1 PLEC DMD MYO18B RMND1 PRKAG2 FOXH1 FHL1 ALDOA FHL2 DNA2 GMPPB NODAL PLN SDHA TAZ SDHB VCL VCP SDHD ALPL CDON DNM2 FKBP14 TBCE PDE11A ADSSL1 POMT2 HNRNPDL DPAGT1 RAF1 CACNA1S COL6A1 HSPG2 COL6A2 TRAPPC11 COL6A3 FLNC PNPLA2 BIN1 COL12A1 VMA21 COL13A1 RAPSN MYOT NEBL SLC25A4 GNE DSG2 CLIP2 CISD2 FKRP SGCA WFS1 SGCB SGCD SGCG ACAD9 FOS SYNE1 KLHL40 RRM2B POLG DOK7 TAF1A B3GALNT2 CAPN3 BAG3 AGPAT2 DOLK DNAJB6 KCNAB2 SHH LAMA4 BAZ1B POMGNT1 LAMB2 XDH CRPPA DNM1L CASQ1 ABCC9 TWNK LAMP2 XK TMEM43 TDGF1 LMNB2 SYT2 CAV1 POMT1 CAV3 TXNRD2 RET PPARG RFC2 CPT2 SIX3 GTF2IRD1 NUBPL SKI DLL1 PPCS SELENON TCAP RBM20 OPA1 CSRP3 MSTO1 NARS2 ALG2 SIL1 NDUFA11 ZIC2 YARS2 ADGRG6 EPG5 CRYAB ERGIC1 TRMU TGIF1 LMOD3 USP8 ORAI1 LIMK1 LDB3 NDUFAF4 GTF2I ABHD5 MTAP ATP6 NDUFAF1 TRNC LMNA COX1 TIA1 COX2 COX3 MTMR14 CYTB MYH14 TRIM32 PABPN1 SLC18A3 TK2 PDE8B GYG1 SLC25A1 FLAD1 ANKRD1 ND1 ISCU SAR1B ND2 SLC22A5 ND4 ND4L ND5 ND6 PRKACA RNR1 PRKAR1A PUS1 GATAD1 LRP4 AGK KBTBD13 TMPO TRNE TRNF CAVIN1 BSCL2 TRNH TRNI ELN HADHA TRNK TRNL1 HADHB SNAP25 RERE CTNS EMD TRNP TRNQ TRNS1 TNNC1 TRNS2 POLG2 TRNT TRNV TNNI3 TRNW TNNT1 TNNT2 SUFU PRDM16 NEXN AGRN TNPO3 HACD1 TBL2 DISP1 MUSK MGME1 LARGE1 MYBPC3 TPI1