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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


HP:0003119: Abnormal circulating lipid concentration
Genes 290
DCAF17 APOA2 PEX5 LMNA POLR3A PNPLA2 PRF1 PHYH APOB PMM2 TNFSF15 TDP1 SMPD1 PEX1 CPT2 PEX6 PIGT LMNA BSCL2 SPINK1 CYP19A1 XRCC4 ABCC8 HSD3B7 ABCG8 ACADVL LDLR AGPAT2 ADCY3 TTPA CETP LIMK1 OCRL TBL2 PEX2 BSCL2 UCP2 GK SLC29A3 SLC37A4 NADK2 ZMPSTE24 MCFD2 LTC4S CETP PEX10 MYO5A TRNL1 PSMB8 LMNA GPIHBP1 LMNB2 DGAT1 SLC12A1 TFG SC5D PEX19 PEX10 LCAT ACAD9 ACAD8 AR LMNA PEX2 MEF2A CTRC PEX7 RAI1 PIK3R5 CEP19 EBP PYGL ACADL BSCL2 POU2AF1 LIPE CFH APOB CLIP2 ACADM PEX5 FHL1 AEBP1 CAVIN1 ANGPTL3 PSMB9 HMGCL DHCR24 FOS FECH TMEM199 GHR PLVAP CYP11A1 LMNA DHCR7 XRCC4 SMPD1 SGPL1 EBP CCT5 PIGH MC4R APOA5 IL12RB1 IRF5 CAV1 STX11 DHCR7 ACAD8 IL12A TRNK AGL POLD1 SLC25A20 PPP1R17 ALMS1 ABHD5 UBE3B LRP6 APOA5 PRSS1 ABCA1 DYRK1B CCDC115 NGLY1 SYNE1 RAI1 LIPA APOA1 ALB FLII PEX7 LDLRAP1 SYNE2 TNPO3 LEPR MSMO1 TMEM43 LCAT FBN1 LDLR GLA SAR1B OCRL ABCG8 KCNJ11 TRMU ABCA1 LEP CAV1 NPC2 HAVCR2 BSCL2 LMNA COG4 ABCD1 IQSEC2 SLC25A13 LMNA GHR LPL UBR1 PEX13 PHKG2 SAR1B PEX11B APTX SLC25A13 CIDEC TBCK ALMS1 XIAP PPARG KCNJ1 PNPLA2 NPHS1 DLD AGL AKT2 GTF2I PEX1 ABCA1 POLR3A NPC1 CTNS SLC37A4 LIPC LMNA SLC25A13 JAG1 ZMPSTE24 LIPA PSMB4 MTTP PHKA2 NUP107 SLC7A7 LIPE ACTN4 CFHR1 APOE ABCA1 PEX14 TRNE APOC3 ACADVL EMD LPL APOC2 NUP107 HMBS CAV1 LDLRAP1 RAI1 LMNA ELN LMAN1 PEX26 ALB PEX19 RAB27A CYP27A1 CFHR3 LMNA TANGO2 ACOX2 FLCN CAVIN1 EPHX2 PPARG CYP7A1 PLIN1 BAZ1B SLC52A1 DEAF1 PEX5 GYS2 SLC22A5 HADH CPT1A NSDHL G6PC PCSK9 ZMPSTE24 PPARG APOC3 HNF1A TRNE NSMCE2 GPD1 CAV3 PANK2 RFC2 HNF4A UNC13D SLC25A13 MMEL1 NPHS2 PEX12 PEX16 PHKA2 PHKG2 TDP1 RSPO1 LMNA PLA2G4A ACADM PCSK9 DCAF17 APOB STXBP2 CIDEC PLA2G7 LBR SPIB NADK2 TANGO2 CYP11A1 PLIN1 PNLIP LCAT CPT1A ABCG5 PEX3 GTF2IRD1 PEX12 AGPAT2 CYP27A1 SETX