SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02929706

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Effectiveness of Thiopurine Dose Optimization by NUDT 15 R139C on Reducing Thiopurine-induced Leucopenia in Inflammatory Bowel Disease

NUDT15 R139C was comfirmed to be associated with thiopurine-induced leukopenia inflammatory bowel disease (IBD) cohort.The present study aim to explor the following questions:can optimizing thiopurine dose by NUDT15 genotype reduce thiopurine-induced leucopenia?What is the influence of this optimizing strategy on clinical outcome?Thus,we conduct a randomised controlled study.Subject in the conventional group detect NUDT15 genotype before thiopurine use and optimise dosage according to the genotype.While the subjects in the control group follow the conventional monitor strategy.The primary endpoint was the rate of leukopenia.The secondary endopoint was the efficacy of thiopurine.The follow up duration was 1 year.

NCT02929706 Thiopurine-induced Leukopenia
MeSH: Intestinal Diseases Inflammatory Bowel Diseases Leukopenia
HPO: Abnormal intestine morphology Inflammation of the large intestine Leukopenia

1 Interventions

Name: Pre-genotype NUDT15 and optimize azathioprine dosage

Description: Pre-genotype NUDT15 and optimize azathioprine dosage.The wild type use azathioprine(Imuran,2-2.5mg/kg/d),the CT genotype use half dose of azathioprine(Imuran,1-1.5mg/kg/d).The TT genotype avoid use of azathioprine.

Type: Genetic

intervention group


Primary Outcomes

Measure: difference of incidence of leucopenia ADR

Time: 1 year

Purpose: Prevention

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 R139C

Effectiveness of Thiopurine Dose Optimization by NUDT 15 R139C on Reducing Thiopurine-induced Leucopenia in Inflammatory Bowel Disease. --- R139C ---

Pre-genotype NUDT 15 R139C on Reducing Thiopurine-induced Leucopenia in Inflammatory Bowel Disease NUDT15 R139C was comfirmed to be associated with thiopurine-induced leukopenia inflammatory bowel disease (IBD) cohort.The present study aim to explor the following questions:can optimizing thiopurine dose by NUDT15 genotype reduce thiopurine-induced leucopenia?What is the influence of this optimizing strategy on clinical outcome?Thus,we conduct a randomised controlled study.Subject in the conventional group detect NUDT15 genotype before thiopurine use and optimise dosage according to the genotype.While the subjects in the control group follow the conventional monitor strategy.The primary endpoint was the rate of leukopenia.The secondary endopoint was the efficacy of thiopurine.The follow up duration was 1 year. --- R139C ---

Pre-genotype NUDT 15 R139C on Reducing Thiopurine-induced Leucopenia in Inflammatory Bowel Disease NUDT15 R139C was comfirmed to be associated with thiopurine-induced leukopenia inflammatory bowel disease (IBD) cohort.The present study aim to explor the following questions:can optimizing thiopurine dose by NUDT15 genotype reduce thiopurine-induced leucopenia?What is the influence of this optimizing strategy on clinical outcome?Thus,we conduct a randomised controlled study.Subject in the conventional group detect NUDT15 genotype before thiopurine use and optimise dosage according to the genotype.While the subjects in the control group follow the conventional monitor strategy.The primary endpoint was the rate of leukopenia.The secondary endopoint was the efficacy of thiopurine.The follow up duration was 1 year. --- R139C --- --- R139C ---

Inclusion Criteria: - diagnosis of IBD with indication of the use of thiopurine Exclusion Criteria: - Contraindication of thiopurine - Previous use of thiopurine - co-treatment with 5-ASA or allopurinol Inclusion Criteria: - diagnosis of IBD with indication of the use of thiopurine Exclusion Criteria: - Contraindication of thiopurine - Previous use of thiopurine - co-treatment with 5-ASA or allopurinol Thiopurine-induced Leukopenia Intestinal Diseases Inflammatory Bowel Diseases Leukopenia We included patients diagnosis of IBD (>18 yrs old) with indication of the use of thiopurine.Group A (intervention): AZA dose optimization by testing for NUDT15 R139C- testing results will be informed.Group B (control):AZA dose optimization according to standard guideline - testing results will not be informed.The participants will be followed for 9 month. --- R139C ---



HPO Nodes


HPO:
Abnormal intestine morphology
Genes 580
PCSK1 MKKS EPHX1 PIGN CDKN2A TMEM67 ASXL1 SLC29A3 ERCC2 SF3B4 AMER1 BRIP1 ERCC4 ABL1 ZMPSTE24 HLA-B PDGFRA MNX1 CENPF PDGFRB LEMD3 HLA-DPA1 HLA-DPB1 ENPP1 AMACR SMC1A HLA-DRB1 RPS6KA3 CFTR NCF1 ACTA2 TMEM216 SLC6A19 ZFP57 BLNK NAA10 PEX1 PEX6 ACTG2 DNAJC21 PEX10 HMBS MMP21 PEX12 PEX13 PEX14 MCM6 RPS19 RPS20 EWSR1 ATP8B1 WNT4 EYA1 ACVRL1 RREB1 MDM2 TRIP13 F5 CHRM3 KLRC4 F12 F13A1 MEFV NLRC4 ACOX2 F13B HNRNPU AXIN2 HIRA ABCB4 CDC45 FANCA FANCC FANCD2 GREB1L FANCE FAH FANCB DACT1 FANCF FANCG SAA1 LONP1 ARID1B AP1S1 FBN2 DLC1 SALL1 KITLG MBTPS2 CIITA COG6 PIK3CA AGA PIK3R1 HPGD SHPK RECQL4 HPS1 UFD1 ARL13B MITF PKD1 GPC4 PEX16 MLH1 TJP2 CC2D2A KMT2A LMOD1 AK2 CYP7B1 ALG8 FGF8 PLAGL1 COL14A1 CCR1 AKT1 NOP10 CCR6 FGFR1 FGFR3 FGFR2 PLCG2 MAD2L2 PLG PIBF1 TRMT5 LTBP4 EIF2AK3 KDM6A NIPBL SEC23B SDHA FOXF1 SDHB SDHC SDHD OPLAH MPI FOXE1 COL3A1 PMS1 COL5A1 FLI1 NDUFB11 FLNA SEMA3C FRAS1 CLCA4 PMS2 FBLN5 CCDC22 HYOU1 PNLIP WAS COMP COMT WIPF1 ADAMTS3 CLIP2 CISD2 CTC1 PTF1A WFS1 WHCR NSD2 POLA1 INPP5E POLD1 POLE RRM2B POLG PEX3 EFEMP2 CEP290 SH3KBP1 ARX FERMT1 POLR1C KCNAB2 WT1 APC ITGA8 TMEM138 COX7B SHH AIRE PORCN POU2AF1 XIAP SI TWNK SLC39A4 RFX6 ARMC9 MSH2 CHD7 MSH3 SIN3A MINPP1 XRCC2 XRCC4 IDS SIX1 SIX3 FANCM GTF2IRD1 SKI PIGV FAS NHP2 SKIV2L FASLG CREBBP ZAP70 SH2B1 SLC2A2 PEX26 ZIC2 SLC5A1 FAN1 MST1 SLC6A8 PACS1 HSD3B7 ARL3 MLH3 SLC9A3 NPHP3 MMEL1 SLC10A2 GPIHBP1 SPINT2 SEC24C COX1 COX2 UBE2T COX3 ARVCF ASCL1 RFXANK TP63 SLCO2A1 IGHM TTC37 C12ORF65 ND1 SETBP1 ND4 ND5 ND6 LPIN2 SNAI2 CEP41 PTCH2 PTRH2 MTTP B9D1 PRKAR1A ABCB11 FLCN TRNE PRKCD TRNF CTBP1 SMO CCN2 CAVIN1 TRNH CTLA4 TRNK IGLL1 TRNL1 RERE CTNNB1 TRNQ TRNS1 TRNS2 TRNW SUFU CEP57 IL2RA PRDM16 PALLD SLX4 MUSK NEUROG3 MUTYH DGAT1 MVK SEMA3E MASP2 CYBA CYBB MYC IL10 CEP104 GABRD IL10RA IL10RB MYCN MYD88 SOX10 UBR1 IL12A IL12RB1 TCTN3 PRSS1 KIF1BP MYH11 DDX59 AHI1 PRTN3 ATP7A PLVAP DIS3L2 MYLK RIPK1 SPIB ATRX SPINK1 CHST14 MYO5B RTEL1 TMEM237 ERAP1 INHBA MYOD1 ZNF423 PIEZO1 GJB6 CYBC1 B2M CYP27A1 BAAT KIAA0586 SRC GAS1 HDAC8 AKR1D1 GATA1 CPLX1 GATA6 CD55 BBS1 ITGA6 SRP54 FGFRL1 PTPN22 IRF5 NCF2 NCF4 SLC46A1 ISL1 KEAP1 DCC PEX11B SRCAP PTCH1 PTEN BCOR GDF2 SLC30A2 NSUN2 ITGB2 ITGB4 GDNF RNF43 ZEB2 ZBTB24 BDNF FREM1 STAT1 STAT3 MKS1 STAT4 JAK2 CBLIF JAK3 STK11 NEK1 BMPR1A GJB2 STX1A STX3 CEP120 ANTXR2 GLA GPC3 BRCA1 BRCA2 PMPCA TINF2 KLHL7 WASHC5 FGF20 CCDC47 CXCR4 GLI2 ABCC8 DHCR7 DHCR24 BTK KCNJ11 BUB1 IL21 DHODH BUB1B CFC1 VPS13A PEX19 PEX2 SERPING1 PEX5 HYLS1 DKC1 ALDH18A1 C1R KIAA0556 C4A RBM8A ADAM17 GNAS SEMA4A COX4I2 STRA6 DMP1 TMEM231 FOXH1 PHOX2B CPLANE1 MAP3K7 HYMAI NODAL KIT MYRF TNFSF15 MED12 PIGO TCTN1 IL23R TBX1 NOTCH2 NOTCH3 RAC2 CDON TBCE GP1BB DNMT3B SPINK5 RAD21 FOXP3 RAD51 RAD51C NPHP1 KRAS TCF4 EFL1 FAT4 TCF3 B3GLCT RAPSN RPGRIP1L RARB CARMIL2 NRAS RHBDF2 USB1 TCOF1 NRTN DOCK8 DYNC2H1 GPR35 NTHL1 TMPRSS6 MYO1H DOK7 UBE3B L1CAM KAT6A NUP88 BAZ1B FARSB B3GALT6 CASP10 SALL4 FANCL TDGF1 OCRL CAV1 LBR RET RFC2 WRAP53 SLC7A7 ECE1 TYMP LCT DLL1 TEK CCNQ TERC AAGAB TERT RFX5 RFXAP TFAP2A DICER1 JMJD1C ARPC1B PALB2 LETM1 EDN3 EDNRB RFWD3 KIF7 TGFB1 TTC7A ERGIC1 RMRP TGFBR2 POLR1D TGIF1 MSH6 RASGRP1 MLXIPL LIG4 SEMA3D LIMK1 LIPA KLLN CD3G KMT2D GTF2I HMGA2 LMNA SMC3 CDCA7 GUCY2C SETD5 IL12A-AS1 VANGL1 CCBE1 SBDS FANCI SAR1B TLR4 CHEK2 LRP2 LRRC8A CD79A CD79B UBAC2 PARN HABP2 CLMP ALG3 PAX3 ELN TNFAIP3 GREM1 LRBA DCTN4 TNFRSF1A BUB3 HBB ENG EPCAM CSPP1 HCCS TNXB TNPO3 TBL2 EP300 DISP1 TP53 SMAD4 TCTN2 HELLS
Inflammation of the large intestine
Genes 43
TGFB1 IL10RA IL10RB MST1 XIAP CASP10 PRKCD RASGRP1 TCF4 NCF4 SLC9A3 PLCG2 TNFAIP3 LRBA CARMIL2 GPIHBP1 WAS WIPF1 RIPK1 FAS SKIV2L FASLG CIITA MAP3K7 RTEL1 COG6 RFX5 RFXAP GPR35 POLA1 ARPC1B ZAP70 RFXANK F13A1 NLRC4 STAT1 F13B OPLAH HPS1 IL21 MASP2 FERMT1 FOXP3
Leukopenia
Genes 163
RAD51 MYC RAD51C DOCK2 TBXAS1 NPM1 TPP2 FOXN1 RAG1 RAG2 FAT4 TCF3 RPL35A BRIP1 EOGT ERCC4 ZBTB16 ATP6AP1 SAMD9 RARA WAS WIPF1 ADAMTS3 TCN2 TNFSF12 RTEL1 DLL4 DOCK8 VPS45 HLA-DRB1 SMARCAL1 ACP5 PSMB4 NUMA1 GATA2 PSMB9 GBA TCIRG1 SRP54 CASP10 NBN IKZF1 FANCL SLC46A1 HMGCL CHD7 TMEM173 EXTL3 NABP1 MAGT1 LCK XRCC2 XRCC4 SLC7A7 PTEN FANCM FAS ADA FASLG CR2 TERC SP110 TBL1XR1 TERT ADA2 RFX5 LYST RFXAP ZAP70 GFI1 LEP ZBTB24 LEPR PALB2 MYSM1 STAT1 PGM3 RFWD3 STAT5B EPG5 TFR2 MSN FANCA FANCC IVD TGFB1 FANCD2 FANCE STK4 UNC119 JAK3 RMRP FANCB FANCF RASGRP1 FANCG CORO1A BLOC1S6 CD3D CD3E CD3G CD247 TRNT1 BCL11B SARS2 ICOS PTPRC CD8A BRCA1 UBE2T CD19 G6PC3 BRCA2 MS4A1 TINF2 CIITA DCLRE1C CDCA7 ARHGAP31 MTHFD1 CXCR4 PIK3CD CCBE1 SGPL1 PIK3R1 PRF1 FANCI RFXANK IGHM BTNL2 SCARB2 NFKB1 NFKB2 RBPJ ERCC6L2 TNFRSF13C PRKAR1A ELANE TNFRSF13B DKC1 FIP1L1 AK2 PRKCD CD81 CTLA4 ATM TNFAIP3 MAD2L2 CTPS1 NHEJ1 DOCK6 IL2RA IL2RG SLX4 VPS13B MMUT NOTCH1 IL7R SEMA3E PML PNP DNMT3B HELLS