SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02723110

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Defining the Physiological Mechanisms of Risk Genes for Hyperglycaemia, Insulin Resistance and Type 2 Diabetes

Recent genetic association studies have identified variants in the Peptidyl-Glycine alpha-amidating mono-oxygenase (PAM) gene that increase the risk of diabetes likely through a defect in beta-cell function. This has been followed up and supported by novel kinetic assays and cellular studies. This investigation will recall heterozygous carriers of the risk allele at rs78408340 and age, BMI and gender matched controls from the Oxford Biobank. The study will compare the incretin effect, glucagon-like peptide-1(GLP-1), insulin, glucose levels and PAM protein activity in individuals both with and without the risk variant. The aim of the study is to gain mechanistic insight into the effect of the variant on human physiology and diabetes pathogenesis.

NCT02723110 Type 2 Diabetes
MeSH: Diabetes Mellitus Diabetes Mellitus, Type 2 Insulin Resistance Hyperglycemia
HPO: Diabetes mellitus Hyperglycemia Insulin resistance Postprandial hyperglycemia Type II diabetes mellitus

2 Interventions

Name: 4 Hour Frequently Sampled Oral Glucose Tolerance Test

Description: Blood glucose level(BGL) every 5 min, blood for hormone, biochemical analysis at -15,0,15,30,45,60,90,120,180, 240

Type: Other

rs78408340 heterozygous carriers homozygous non-risk allele carriers

Name: Isoglycaemic Clamp

Description: Glucose infusion over 4 hours to reproduce OGTT glucose curve to allow measurement of incretin effect. BGL every 5 min, blood for hormone, biochemical analysis at -15,0,15,30,45,60,90,120,180, 240

Type: Other

rs78408340 heterozygous carriers homozygous non-risk allele carriers


Primary Outcomes

Description: Will be calculated from the amount of IV glucose required to reproduce OGTT glycaemic profile

Measure: Calculated Incretin Effect

Time: 3 months

Secondary Outcomes

Measure: Insulin concentration

Time: 3 months

Measure: Glucose concentrations

Time: 3 months

Measure: GLP-1 (glucagon-like peptide-1) amidated and unamidated concentration

Time: 3 months

Description: This assay is based off the protocol in the published literature, and is based on the turnover of radio-labelled substrate to quantify the amidating ability of the PAM enzyme

Measure: PAM enzyme activity assay

Time: 3 months

Time Perspective: Prospective

Case Control


There is one SNP

SNPs


1 rs78408340

This investigation will recall heterozygous carriers of the risk allele at rs78408340 and age, BMI and gender matched controls from the Oxford Biobank.



HPO Nodes


HPO:
Diabetes mellitus
Genes 326
SOX2 MKRN3 SOX3 MKKS SNORD115-1 SPATA7 CDKN2A HFE CERKL UBR1 PRPF31 LRAT PRSS1 TREX1 PRSS2 IFT140 ARL2BP GLRX5 SLC29A3 MAK AHI1 ABCA4 PDE4D ZBTB20 PDE6A PDE6G ZMPSTE24 IMPDH1 CEL STUB1 SPINK1 RTEL1 PDE6B LEMD3 INS HLA-DQB1 GJB4 IFT172 AMACR KIZ CDHR1 HLA-DRB1 CYP19A1 CFTR DHX38 MAFA GAS1 INSR ZFP57 MC4R GATA3 CTRC GATA6 PDX1 IPW PEX1 BBS1 PWRN1 PEX6 BBS2 DNAJC21 PEX10 CDH23 SRP54 DHDDS NDN PRPF6 GCK NDP KCTD1 AGBL5 GPR101 PTCH1 HNF4A ADAR TTPA TUB SNORD116-1 HESX1 STAT1 STAT3 TULP1 BLK BLM ARL6 IFIH1 TTC8 GJA1 PROM1 NEK2 GJB3 SAG FBN1 NEUROD1 SARS2 PNPLA6 BRCA1 ALMS1 BRAF BRCA2 PROKR2 CLCNKB TINF2 KLHL7 REEP6 FAM161A PIK3R1 GLI2 ABCC8 KCNJ11 RNASEH2C ARNT2 NPAP1 SCAPER FSCN2 DCAF17 AHR PRCD DKC1 FGF8 PLAGL1 AKT2 NOP10 FGFR1 PLCD1 GNAS PWAR1 SEMA4A HERC2 MERTK FOXH1 PLIN1 HYMAI NODAL USH2A CLRN1 CNGB1 CNGA1 EIF2AK3 MOG CDON CA4 IMPG2 PDE11A FOXP3 FOXC2 HJV PROK2 RNASEH2B KRAS TCF4 KLF11 EFL1 HNF1A BEST1 HNF1B PNPLA2 NR2E3 MAGEL2 POC1A OFD1 SLC25A4 USB1 NRL CLIP2 APOA5 CISD2 RNASEH2A CTC1 PTF1A WFS1 GPR35 POLD1 FOS RRM2B POLG AGPAT2 RBP3 WRN SLC19A2 HGSNAT GLIS3 SHH AIRE KIAA1549 FUZ BAZ1B RDH12 POMGNT1 PRPH2 ARHGEF18 DNM1L CP TWNK CPA1 CASR PCARE SAMHD1 TDGF1 AIP CAV1 PSTPIP1 FXN APOE IDH3B PPARG RFC2 XRCC4 WRAP53 SIX3 GTF2IRD1 NSMCE2 PRPF8 DLL1 NHP2 TERC TERT EDA RGR SLC7A14 AR LEP OPA1 LEPR PALB2 POLR3A RHO CRB1 ZIC2 MKRN3-AS1 CRX RLBP1 TTC7A PPP1R3A CNBP MST1 ERGIC1 LHX1 TGIF1 USP8 MLXIPL LIG4 LIMK1 EYS ARL3 LIPE OTX2 IGF1R GTF2I HMGA2 ATP6 TRNC SLC12A3 LMNA COX1 COX2 COX3 GUCA1B IFT88 CYTB SLC16A2 PRPF4 PRPF3 ELMO2 PDE8B VANGL1 SBDS EIF2S3 IER3IP1 ZNF408 CIDEC ND1 ARMC5 ND4 ND5 ND6 PRKACA PRKAR1A NKX2-5 APPL1 TRNE TRNF ROM1 ZFYVE26 PARN CAVIN1 BSCL2 TRNH RP9 RP1 ELN TRNK PAX4 RP2 TRNL1 RPGR ATM HAMP CTNS CTNNB1 C8ORF37 TRNQ TRNS1 TRNS2 POLG2 TRNV TOPORS TRNW KDSR HBB SUFU IL2RA RPE65 DNAJC3 SNRNP200 SNRPN PALLD TBL2 DISP1 EDA2R NEUROG3 TP53 CEP19 SMAD4 PCNT ZNF513
Hyperglycemia
Genes 37
BLK GATA6 PDX1 CACNA1S APPL1 PLAGL1 KLF11 HNF1A LRPPRC RFX6 GCK PAX4 KCNE3 NEUROD1 KCNJ18 PPARG ZMPSTE24 CEL LMNA HNF4A HYMAI ACAT1 PTF1A EIF2AK3 INS PIK3R1 GLI3 ABCC8 SHPK GYS2 STAT3 KCNJ11 ARMC5 SCN4A INSR GABRA3 ZFP57
Insulin resistance
Genes 56
BLK PPP1R3A KLF11 HNF1A HNF1B IGF1 LIPE NEUROD1 IGFALS ZMPSTE24 SLC12A3 CEL LMNA ALMS1 CLCNKB PTF1A INS PIK3R1 POLD1 FOS ABCC8 CYP19A1 CIDEC KCNJ11 AGPAT2 INSR ZFP57 WRN DCAF17 GATA6 PDX1 MFN2 APPL1 PLAGL1 AKT2 CAVIN1 BSCL2 HSD3B2 DBH GCK LMNB2 PAX4 CAV1 HSD11B1 PPARG XRCC4 NSMCE2 PLIN1 HNF4A HYMAI EIF2AK3 LEP LEPR STAT3 CEP19 PMM2
Postprandial hyperglycemia
Genes 8
SHPK GYS2 KCNE3 SCN4A CACNA1S KCNJ18 INSR GABRA3
Type II diabetes mellitus
Genes 152
MKRN3 SNORD115-1 SPATA7 CERKL PRPF31 LRAT KLF11 IFT140 HNF1A BEST1 HNF1B ARL2BP NR2E3 GLRX5 MAK AHI1 MAGEL2 ABCA4 PDE6A PDE6G IMPDH1 OFD1 STUB1 SPINK1 NRL CLIP2 PDE6B IFT172 AMACR KIZ CDHR1 CYP19A1 DHX38 INSR RBP3 WRN MC4R HGSNAT PDX1 IPW KIAA1549 PWRN1 BBS2 BAZ1B PEX10 RDH12 POMGNT1 PRPH2 DHDDS ARHGEF18 PCARE NDN PRPF6 GCK IDH3B AGBL5 RFC2 XRCC4 GTF2IRD1 PRPF8 RGR TUB SLC7A14 AR SNORD116-1 TULP1 POLR3A RHO CRB1 MKRN3-AS1 CRX BLM RLBP1 PPP1R3A ARL6 TTC8 PROM1 LIG4 NEK2 LIMK1 EYS ARL3 SAG FBN1 GTF2I PNPLA6 SLC12A3 LMNA COX1 ALMS1 BRAF COX2 COX3 GUCA1B CLCNKB IFT88 KLHL7 PRPF4 PRPF3 REEP6 FAM161A ABCC8 ZNF408 ND1 ND4 ND5 ND6 NPAP1 SCAPER FSCN2 AHR PRCD TRNE TRNF ROM1 AKT2 TRNH RP9 PLCD1 RP1 ELN TRNK PAX4 RP2 TRNL1 RPGR ATM PWAR1 SEMA4A CTNNB1 C8ORF37 HERC2 TRNQ MERTK TRNS1 TRNS2 TOPORS TRNW USH2A RPE65 CLRN1 CNGB1 CNGA1 SNRNP200 SNRPN TBL2 MOG CEP19 CA4 IMPG2 PCNT ZNF513