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Report for Clinical Trial NCT00588172

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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
MeSH: Diabetes Mellitus, Type 2
HPO: Type II diabetes mellitus

1 Interventions

Name: Metformin

Description: 1000mg bid for 1 week

Type: Drug

1 2


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

Purpose: Basic Science

Allocation: Non-Randomized

Parallel Assignment


There are 4 SNPs

SNPs


1 G174S

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 --- --- G174S ---


2 G401S

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 ---


3 G465R

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 ---


4 R61C

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 ---



HPO Nodes


HPO:
Type II diabetes mellitus
Genes 182
SNRPN USH2A PDE6A IDH3A LIPC SNORD116-1 GTF2I GCGR C8ORF37 BAZ1B PCARE TRNH RP1 PRPF6 LMNA IPW IFT88 PDE6B ZNF408 ABCC8 RGR TTC8 PROM1 PDX1 AR ND4 NPAP1 HGSNAT NEK2 RFC2 CA4 KLF11 SEMA4A BEST1 TRNL1 RHO IDH3B MKRN3 SCAPER PPARG PCNT PEX10 TUB XRCC4 SNRNP200 SLC2A2 CEP19 CRB1 ABCA4 EYS MAPK8IP1 TRNQ TCF7L2 POLR3A RP9 GTF2IRD1 TRNE FBN1 PRPF4 AKT2 ZNF513 ARL6 TRNS2 RDH12 CRX STUB1 ARL3 NEUROD1 KLHL7 RBP3 SPINK1 NR2E3 ALMS1 TRNS1 KCNJ11 LIMK1 INSR HNF1A ARL2BP BRAF RPE65 AHR PWRN1 GLRX5 PRPF31 MAK PNPLA6 PRCD RLBP1 HNF1B AHI1 IMPDH1 TRNK AGBL5 TRNL1 TULP1 DHX38 GPD2 HMGA1 ATM NDN COX1 FAM161A NRL DHDDS CDHR1 MAGEL2 MKRN3-AS1 CLIP2 CTNNB1 AIP TRNF SLC12A3 IFT140 SLC30A8 RP2 POLA1 ND1 REEP6 IMPG2 ELN PWAR1 LIG4 RETN BLM PDX1 CNGA1 TRNW COX3 IRS1 INSR ROM1 BBS2 PRPF3 GCK KIZ TBL2 COX2 WFS1 GCK PRPH2 LRAT ABCC8 SNORD115-1 PRPF8 SPATA7 ENPP1 GUCA1B MEN1 IRS2 MERTK POMGNT1 HNF4A WRN ND6 HNF1A PTPN1 PPP1R3A CERKL CLRN1 PAX4 SLC7A14 KIAA1549 MC4R IGF2BP2 PDE6G ARHGEF18 SAG MOG AMACR TOPORS MTNR1B CLCNKB ND5 PLCD1 OFD1 FSCN2 IFT172 HERC2 CYP19A1 RPGR CNGB1