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Report for Mutation E167K

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There is one clinical trial.

Clinical Trials


1 Genetic Regulation of Lipid Pathways Contributing to Non-alcoholic Fatty Liver and Atherogenic Dyslipidemia

The aims of the study are: 1. To investigate if carriers of apolipoprotein (apo) CIII loss-of-function (LOF) mutations produce less apo-CIII that results in reduction of large very low-density lipoprotein (VLDL) particle secretion as compared to non-carriers of these variants and compare the results with carriers of apo-CIII gain-of-function (GOF) to elucidate the role of apo-CIII in hepatic lipid metabolism. 2. To study if carriers of the TM6SF2 E167K and PNLPLA3 I148M mutations produce less large VLDL particles to transport fat out of the liver as compared to non-carriers. 3. To test whether the specific mutations in the apo-CIII, TM6SF2 and PNLPLA3 genes are reflected in changes of liver de novo lipogenesis (DNL), liver fat, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), plasma lipid and apolipoprotein kinetics and fasting concentrations in carriers of the TM6SF2 E167K and PNLPLA3 I148M mutations as compared to non-carriers. 4. To study the effects of APOE, angiopoietin (ANGPTL3 and ANGPTL8) or endothelial lipase (LIPG) genotypes on liver fat metabolism, lipid and apolipoprotein metabolism and lipid phenotypes.

NCT04209816 Non-alcoholic Fatty Liver Atherogenic Dyslipidemia Insulin Resistance Diagnostic Test: Lipoprotein kinetics
MeSH: Fatty Liver Non-alcoholic Fatty Liver Disease Insulin Resistance Dyslipidemias
HPO: Abnormal circulating lipid concentration Hepatic steatosis Insulin resistance

2. To study if carriers of the TM6SF2 E167K and PNLPLA3 I148M mutations produce less large VLDL particles to transport fat out of the liver as compared to non-carriers. --- E167K ---

3. To test whether the specific mutations in the apo-CIII, TM6SF2 and PNLPLA3 genes are reflected in changes of liver de novo lipogenesis (DNL), liver fat, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), plasma lipid and apolipoprotein kinetics and fasting concentrations in carriers of the TM6SF2 E167K and PNLPLA3 I148M mutations as compared to non-carriers. --- E167K ---

Inclusion Criteria: - persons who have provided written consent - apo-CIII loss-of-function mutation (heterozygous) or apo-CIII gain-of-function mutations (heterozygous) or TM6SF2 E167K mutation (homozygous) or PNLPLA3 I148M or apoE or LIPG or ANGPTL3 or ANGPTL8 LOF and GOF variants. --- E167K ---

m² at inclusion Exclusion Criteria: - Patients with Type 1 and 2 diabetes, BMI > 40 kg/m2, - ApoE2/2 phenotype, thyrotropin concentration outside normal range, - Lipid-lowering drugs - Blood pressure >160 mmHg systolic and/or > 105 diastolic mmHg - Liver failure or abnormal liver function tests >3 x upper limit of normal - Intestinal disease - Pregnancy, breastfeeding - Patients with volume depletion Inclusion Criteria: - persons who have provided written consent - apo-CIII loss-of-function mutation (heterozygous) or apo-CIII gain-of-function mutations (heterozygous) or TM6SF2 E167K mutation (homozygous) or PNLPLA3 I148M or apoE or LIPG or ANGPTL3 or ANGPTL8 LOF and GOF variants. --- E167K ---

Primary Outcomes

Description: Production rate, mg/day

Measure: Difference in the rate of production of VLDL Apo B

Time: Baseline

Description: Production rate, mg/kg/day

Measure: Difference in the rate of production of VLDL Triglycerides

Time: Baseline

Description: Production rate, mg/kg/day

Measure: Difference in the rate of production of VLDL ApoC-III and apoE

Time: Baseline

Description: Rate of disappearance, pools/day

Measure: Difference in the Fractional Catabolic Rate of VLDL Apo B

Time: Baseline

Description: Rate of disappearance, pools/day

Measure: Difference in the Fractional Catabolic Rate of VLDL Triglycerides

Time: Baseline

Description: Rate of disappearance, pools/day

Measure: Difference in the Fractional Catabolic Rate of VLDL ApoC-III and apoE

Time: Baseline

Description: Measure of newly synthesized triglycerides in VLDL, μmol/l

Measure: Difference in de novo lipogenesis

Time: Baseline

Description: Percentage of liver fat measured with magnetic resonance spectroscopy

Measure: Difference in liver fat

Time: Baseline

Description: Remnant lipoproteins and lipoprotein fraction composition, mg/L

Measure: Difference in atherogenic dyslipidemia

Time: Baseline

Description: Calculated Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

Measure: Difference in insulin resistance

Time: Baseline

Description: ApoA, mg/dl

Measure: Difference in apoprotein A concentration

Time: Baseline

Description: ApoB, mg/dl

Measure: Difference in apoprotein B concentration

Time: Baseline

Description: ApoC, mg/dl

Measure: Difference in apoprotein C concentration

Time: Baseline

Description: ApoE, mg/dl

Measure: Difference in apoprotein E concentration

Time: Baseline

Description: Rate of turnover, pools/day

Measure: Difference in the rate of production and Fractional Catabolic Rate of intermediate-density Apo B

Time: Baseline

Description: Rate of turnover, pools/day

Measure: Difference in the rate of production and Fractional Catabolic Rate of low-density lipoprotein Apo B

Time: Baseline

Description: Measured lipoprotein lipase activity, mU/ml

Measure: Lipolytic activity

Time: Baseline

Description: Measured hepatic lipase activity, mU/ml

Measure: Hepatic lipase activity

Time: Baseline


HPO Nodes


Hepatic steatosis
Genes 137
ATP7B LDLRAP1 MPV17 CLPB APOE APOB SLC40A1 POLG HNF1B COA8 ABCG8 BSCL2 HFE GPD1 BCS1L CIDEC ACAD9 LYRM4 AGPAT2 LMNA LMNB2 PRDM16 CAV1 FOS LMNA TYMP LIPE RERE BCS1L MPV17 BSCL2 CIDEC MCCC1 ACADM PLIN1 SLC25A13 HADHB ETFA CAV1 XRCC4 CPT1A FBP1 PCK1 PTRH2 CEP19 RMND1 LMNA GABRD POLR3A TMEM199 NSMCE2 PPARG ADK ACAD9 LIPA TFAM NGLY1 PMM2 HNRNPA1 VPS33A AKT2 POLD1 MARS1 DDOST TRAPPC11 ETFB ACADVL BSCL2 ALMS1 LMNA LARS1 CPT2 CBS CARS2 COX15 NDUFAF1 LRPPRC ALDOB PCSK9 HNRNPA2B1 TRMU PGM1 NSMCE2 CPT2 LIPE ACOX1 LDLR CYP7A1 MRPL44 PCK2 DNAJC19 LMNA FARSB ABHD5 CAVIN1 PNPLA2 HADH ZMPSTE24 ETFDH ALMS1 PNPLA2 SLC22A5 PHKG2 AGPAT2 DGUOK ATP6AP1 COG6 ABHD5 HADHA PHKA2 SLC40A1 TARS2 LMNA TRAPPC11 PPARG MRPS7 KCNAB2 ACADL HADH SLC25A13 ACADM VCP HNF4A PLIN1 PPARG EARS2 SAR1B CAVIN1 SLC25A13 HSD17B4 DNAJC19 RRM2B SKI CYP19A1 IARS1 POLG ABCG5
Abnormal circulating lipid concentration
Genes 286
CYP11A1 PEX1 LDLR UBR1 APOB BAZ1B PEX7 PNLIP CCDC115 ABCG8 CYP27A1 BSCL2 HNF1A CIDEC AGPAT2 LMNA RAI1 POU2AF1 GHR IQSEC2 RFC2 HMBS LIPE PEX12 BSCL2 ACADM MYO5A APOB SLC25A13 STXBP2 MSMO1 TRMU UBE3B NSDHL CPT1A SLC37A4 DHCR7 CEP19 EMD LMNA ACAD8 SLC25A20 NADK2 TMEM199 NSMCE2 GTF2IRD1 RAI1 TDP1 NGLY1 ABCA1 PMM2 POLD1 OCRL EBP BSCL2 TFG TNFSF15 LCAT HSD3B7 PLA2G4A DYRK1B PCSK9 DHCR24 PYGL TRNK TRNL1 NPC2 ABCC8 CTNS NADK2 LBR ACOX2 PIGH SLC7A7 CYP7A1 TMEM43 JAG1 DEAF1 LEP CLIP2 LMNA PEX5 NPC1 ELN CAV3 FHL1 PRF1 PLVAP FLCN CAVIN1 CETP SMPD1 PNPLA2 PRSS1 LEPR LRP6 APTX LPL STX11 TBL2 ALMS1 LDLRAP1 APOA5 BSCL2 DCAF17 PNPLA2 ZMPSTE24 SLC22A5 PIK3R5 SPIB RSPO1 PHKG2 SLC52A1 ABCA1 CFH PEX26 SETX SLC37A4 EPHX2 LIPC PPARG PEX13 ACADL PEX12 IL12RB1 ABCA1 SLC29A3 ACADM LMNA ANGPTL3 MMEL1 LMNA PLIN1 MTTP SAR1B CAVIN1 PEX3 PEX2 CYP19A1 TNPO3 ABCG5 DGAT1 TTPA SMPD1 CFHR1 LDLRAP1 GTF2I ACADVL HMGCL APOE FECH SGPL1 LMNB2 GPD1 PSMB9 TDP1 LMNA PEX6 NUP107 APOA2 CAV1 NUP107 AR FOS ZMPSTE24 TBXAS1 LMNA UCP2 CIDEC MEF2A PLIN1 PEX5 PPP1R17 ABCD1 CAV1 XRCC4 PEX10 PEX5 ADCY3 HAVCR2 ABCG8 CPT1A CYP27A1 APOB APOC3 LIPA LMNA PEX2 POLR3A TRNE FBN1 PEX10 PPARG XRCC4 ACAD9 LIPA LCAT SYNE1 LCAT DCAF17 SC5D AKT2 G6PC NPHS1 ACADVL ALMS1 LMNA LTC4S CETP LIMK1 PEX11B RAI1 GK APOC3 CCT5 CFHR3 TRNE PCSK9 ALB APOA5 SLC25A13 DHCR7 PSMB8 PSMB4 CPT2 LIPE APOC2 LDLR KCNJ1 SAR1B AGL CAV1 ACAD8 PEX19 CFTR HNF4A COG4 XIAP GHR OCRL LPL SLC12A1 UNC13D CYP11A1 PEX14 HADH NPHS2 POLR3A TANGO2 PEX1 PEX16 IL12A ZMPSTE24 PEX7 PHKA2 RAB27A FLII ACTN4 PHKG2 PANK2 AGPAT2 PHYH GPIHBP1 ALB PEX19 KCNJ11 ABHD5 LMNA PHKA2 GYS2 ABCA1 GLA MC4R SYNE2 LMNA SLC25A13 IRF5 PLA2G7 CTRC APOA1 EBP PPARG SLC25A13 AGL SPINK1 DLD
Insulin resistance
Genes 122
LIPC KCNJ11 HNF1A GCGR STAT3 BSCL2 HSD3B2 ABCC8 AGPAT2 INS LMNA LMNB2 LMNA PDX1 ABCC8 ABCC8 INS CAV1 FOS ZMPSTE24 LMNA HYMAI LIPE BSCL2 CIDEC PLIN1 PPARG HYMAI CAV1 XRCC4 ADCY3 SLC2A2 CEP19 IGFALS LMNA MAPK8IP1 TCF7L2 DBH NEUROD1 NSMCE2 AKT2 PPARG XRCC4 IGF1 GATA6 NEUROD1 GCK AKT2 POLD1 PAX4 BSCL2 ALMS1 LMNA PDX1 PMM2 KCNJ11 HNF1A PTF1A HYMAI PLAGL1 HNF1B KLF11 NSMCE2 PIK3R1 BLK LIPE KCNJ11 GPD2 HMGA1 CEL INSR INSR ZFP57 CAV1 LEP ABCC8 SLC12A3 SLC30A8 EIF2AK3 LMNA GCK PDX1 RETN PDX1 CAVIN1 HNF4A IRS1 PIK3R1 ZFP57 PLAGL1 LEPR KCNJ11 ZMPSTE24 GCK MFN2 WFS1 ALMS1 APPL1 DCAF17 ABCC8 PAX4 ZMPSTE24 HSD11B1 AGPAT2 ENPP1 IRS2 HNF4A WRN PTPN1 PPP1R3A LMNA PAX4 PPARG IGF2BP2 KCNJ11 LMNA MTNR1B CLCNKB PPARG CAVIN1 EIF2AK3 CYP19A1