SNPMiner Trials by Shray Alag

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Report for Mutation G465R

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There is one clinical trial.

Clinical Trials

1 Genetic Variation in OCT1 and Response to Metformin

Type 2 diabetes its microvascular and macrovascular complications have become a major global health problem. Metformin is often used as first-line therapy for this disorder given that it is cheap, may cause weight loss and does not have significant side-effects in healthy patients. On the other hand, as many as one third of all patients with type 2 diabetes initially treated with metformin never achieve a meaningful response to this intervention. Recently, genetic variation in the organic cation transporter 1 (Oct1) gene which encodes a protein, OCT1, mediating metformin uptake by the liver, its primary site of action, has been shown alter metformin action. In Oct1-deficient mice the glucose-lowering effects of metformin are completely abolished. Moreover a polymorphism with a 20% minor allele frequency in Caucasians also alters the effect of metformin on glucose tolerance (the net result of glucose uptake and glucose release) after ingestion of 75g of glucose. However, it is unknown if this polymorphism affects suppression of endogenous glucose production or stimulation of peripheral glucose uptake by metformin, or both, and to what degree. We propose to utilize established methodology to measure glucose turnover in response to a mixed meal to determine how common genetic variation in OCT1 alters response to metformin in healthy volunteers. This will clarify the effect of these variants on response to metformin in humans. The knowledge gained from this study will help to design future studies examining the role of OCT1 genotype in determining initial therapy for type 2 diabetes.

NCT00588172 Type 2 Diabetes Drug: Metformin
MeSH:Diabetes Mellitus, Type 2
HPO:Type II diabetes mellitus

Inclusion criteria: - 1. Heterozygous or homozygous for the nsSNPs R61C, G401S, 420Del, G465R, G174S (see supplementary info (3)) or without any nsSNPs that could potentially alter gene function. --- R61C --- --- G401S --- --- G465R ---

Primary Outcomes

Measure: Change in glucose area under the curve after a mixed meal in response to metformin

Time: before and after 1 week of metformin

Secondary Outcomes

Measure: Change in glucose disappearance and suppression of endogenous glucose production in response to metformin

Time: before and after 1 week of metformin therapy

HPO Nodes

HP:0005978: Type II diabetes mellitus
Genes 184
MKRN3 TRNF BLM BRAF KCNJ11 MKRN3-AS1 ZNF513 FBN1 AKT2 HGSNAT MOG RP1 RDH12 GUCA1B INSR NDN GCK HNF1A LMNA IDH3A ZNF408 SNORD115-1 MAK IFT172 BEST1 CYP19A1 POMGNT1 FSCN2 PWRN1 TRNL1 SLC12A3 ENPP1 CRX GLRX5 AMACR CDHR1 PRPF31 BBS2 CRB1 PTPN1 LIMK1 TBL2 IRS2 HNF1B RP9 PNPLA6 ABCC8 SLC30A8 DMXL2 GTF2I ARL2BP IMPG2 TRNW TRNL1 COX3 ROM1 C8ORF37 PDE6B POLR3A MTNR1B LRAT RBP3 KIZ KLF11 PRPF8 PRPH2 PDE6G TOPORS PEX10 CLRN1 TRNH RPGR COX1 IRS1 ABCC8 HERC2 NRL PDE6A PRPF4 ND1 TUB RHO FAM161A AR RGR HNF1A ND5 ND4 CLCNKB PROM1 COX2 SEMA4A ARL6 MEN1 TRNS2 GCK GPD2 CEP19 SAG ABCA4 MAGEL2 ELN TTC8 TULP1 SNRPN USH2A PRPF6 PWAR1 RPE65 REEP6 CLIP2 IGF2BP2 CNGA1 INSR MERTK AHI1 SPATA7 NPAP1 NR2E3 BAZ1B SNRNP200 PPP1R3A ARHGEF18 DHX38 HNF4A KIAA1549 POLA1 PLCD1 AHR IDH3B PDX1 KLHL7 TRNQ PRPF3 SLC7A14 CNGB1 AIP PDX1 RP2 GCGR WRN RLBP1 MAPK8IP1 MC4R TRNE TCF7L2 SNORD116-1 AGBL5 SLC2A2 IPW RFC2 PAX4 WFS1 CA4 LIG4 TRNK HMGA1 XRCC4 TRNS1 IMPDH1 RETN PPARG IFT140 NEUROD1 ALMS1 SPINK1 PCNT ND6 CAT EYS CTNNB1 NEK2 CERKL LIPC SCAPER PRCD ATM STUB1 PCARE ARL3 IFT88 GTF2IRD1 DHDDS OFD1
Protein Mutations 12
A54T E158K E23K G174S G212A G401S G465R I349V K121Q P12A R230C R61C
SNP 7
rs13266634 rs2266782 rs35652124 rs780094 rs780094s rs78408340 rs7903146