The TCF7L2 Gene: Nutrigenomics and Dietary Prevention of Type 2 Diabetes

Nutrients and chemicals in food are able to regulate expression of genetic elements. Gene-nutrient interaction in response specific diets can increase an individual's risk, shifting the individual from health toward the development of chronic disease. The Transcription Factor 7 Like 2 (TCF7L2) gene may either put individuals at risk for or protect from Type 2 diabetes mellitus in the presence of certain foods. The main purpose of this four-week study is to examine diet-induced gene-nutrient interaction, with a focus on glucose, insulin, inflammation (CRP) and the plasma metabolome in individuals who have either the CC or the TT form of the rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene. The (2) one-week study diets, one Mediterranean diet (MedDiet) based and the other low-fat based will be separated by a (1) week return to a regular habitual diet.

NCT03458494 Type2 Diabetes Glucose, High Blood

MeSH:Diabetes Mellitus, Type 2 Hyperglycemia

HPO:Hyperglycemia Postprandial hyperglycemia Type II diabetes mellitus

2 Interventions

Name: Mediterranean Diet

Name: Low-fat diet

Purpose: Prevention

Allocation: Randomized

Crossover Assignment

There is one SNP

SNPs

1 rs7903146

The main purpose of this four-week study is to examine diet-induced gene-nutrient interaction, with a focus on glucose, insulin, inflammation (CRP) and the plasma metabolome in individuals who have either the CC or the TT form of the rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene.

Plasma glucose levels (mg/dl) will be measured in the fasting state during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP.

Fasting plasma insulin levels (pmol/l) will be measured in the fasting state during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP.

The response of plasma metabolites to the Mediterranean and low-fat diets diet) will be measured using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP.

Fasting plasma concentrations of VLDL in mg/dl, assessed by proton nuclear magnetic resonance (NMR) spectroscopy will be measured during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP.

Fasting plasma concentrations of LDL in mg/dl, assessed by proton nuclear magnetic resonance (NMR) spectroscopy will be measured during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP.

Fasting plasma concentrations of HDL in mg/dl, assessed by proton nuclear magnetic resonance (NMR) spectroscopy will be measured during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP.

Plasma C-reactive protein (mg/dl) will be measured in the fasting state during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP.

The rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene is the most replicated T2D-associated SNP.

For this purpose, a four-week study will be conducted to examine diet-induced gene-nutrient interaction, with a focus on glucose, insulin, and inflammation (CRP) in individuals who have either the CC or the TT form of the rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene.

HPO Nodes

HPO:

HP:0003074: Hyperglycemia

Genes 68

ABCC8 AFF4 INS HNF1A EIF2AK3 LMNA ABCC8 GABRA3 HYMAI PDX1 KCNJ11 PIK3R1 APPL1 LRPPRC PDX1 PTPN22 ABCC8 GCK STAT3 LMNA CACNA1S HNF1A BLK ACAT1 LMNA GATA6 KCNJ11 SCN4A GCK NEUROD1 PLAGL1 GLI3 GYS2 INSR KCNJ11 ABCC8 PAX4 IL6 GCK PPARG KCNJ11 INS ZFP57 PTF1A GYS2 INS KCNJ18 INS RFX6 HNF1A INSR KCNE3 KCNJ11 HNF4A KCNJ11 ARMC5 SHPK KLF11 CACNA1S ITPR3 ZMPSTE24 INSR PDX1 ABCC8 ZFP57 HYMAI INS CEL

Protein Mutations 0

SNP 0

HP:0011998: Postprandial hyperglycemia

Genes 12

SCN4A INSR KCNE3 GYS2 GABRA3 INSR CACNA1S SHPK GYS2 KCNJ18 CACNA1S INSR

Protein Mutations 0

SNP 5

rs12255372 rs780094 rs780094s rs78408340 rs7903146

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 9

rs10401969 rs13266634 rs2266782 rs2854275 rs35652124 rs780094 rs780094s rs78408340 rs7903146