SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01274091

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Gene-diet Interactions

Interactions between genes and environment, i.e. our inherited responses to environmental changes, may be crucial in the development of the common diseases. The investigators were the first to identify PPARG gene as risk gene for type 2 diabetes. The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. However, this effect on seems to depend on intervention and age. In this study the effects of diets high with saturated fatty acids (SAFA) and polyunsaturated fatty acids (PUFA) are compared in subjects carrying either Pro12Pro or Ala12Ala genotype of the PPARG gene. Aim of the study: To test if subjects with Pro12Pro and Ala12Ala genotypes respond differentially to a diet supplemented with high saturated (SAFA) or polyunsaturated fat (PUFA). Hypotheses: 1. Specific: Subjects with the Ala12Ala genotype will be more sensitive to dietary modification, and therefore respond more favorably to PUFA diet 2. More general: Dietary instructions individually tailored according to the genotype would allow better treatment of obesity and diabetes

NCT01274091 Insulin Sensitivity
MeSH: Hypersensitivity Insulin Resistance
HPO: Allergy Insulin resistance

2 Interventions

Name: PUFA-diet

Description: Diets will contain 30% of energy as fat, 18% as protein and 52% as carbohydrates: polyunsaturated fatty acid diet (PUFA) will have P/S ratio 1.0.

Type: Other

P/S-ratio 1.0

Name: SAFA-diet

Description: Diets will contain 30% of energy as fat, 18% as protein and 52% as carbohydrates: Saturated fatty acid diet (SAFA) will polyunsaturated/saturated (P/S) ratio of 0.3.

Type: Other

P/S-ration 0.3


Primary Outcomes

Description: insulin sensitivity measured by oral glucose tolerance test at the beginning of the first, randomised diet

Measure: insulin sensitivity

Time: week 0

Description: insulin sensitivty measured by oral glucose tolerance test after the first diet

Measure: insulin sensitivity

Time: week 8

Description: Insulin sensitivity measured by oral glucose tolerance test in the beginning of the second, randomised diet

Measure: insulin sensitivity

Time: week 10

Description: insulin sensitivity measured by oral glucose tolerance test after the second diet

Measure: insulin sensitivity

Time: week 18

Secondary Outcomes

Measure: peripheral blood mononuclear cell gene expression

Time: week 8

Measure: peripheral blood mononuclear cell gene expression

Time: week 18

Description: serum lipids, including serum lipidomics and fatty acid composition

Measure: serum lipids

Time: week 8

Description: serum lipids, including serum lipidomics and fatty acid composition

Measure: serum lipids

Time: week 18

Description: inflammation measured as serum cytokines and adipose tissue inflammation

Measure: inflammation

Time: week 8

Description: inflammation measured as serum cytokines and adipose tissue inflammation

Measure: inflammation

Time: week 18

Description: energy expenditure and the rates of substrate oxidation

Measure: energy expenditure

Time: week 8

Description: energy expenditure and the rates of substrate oxidation

Measure: energy expenditure

Time: week 18

Measure: insulin secretion

Time: week 8

Measure: insulin secretion

Time: week 18

Measure: adipose tissue gene expression

Time: week 8

Measure: adipose tissue gene expression

Time: week 18

Purpose: Prevention

Allocation: Randomized

Crossover Assignment


There is one SNP

SNPs


1 P12A

The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. --- Pro12Ala ---

Inclusion Criteria: - BMI >20kg/m2 <29kg/m2 - Pro12Pro and Ala12Ala genotypes of PPARG Pro12Ala polymorphism - participation to METSIM-study (METabolic Syndrome in Men, currently >10000 men included from the population living in Kuopio, principal investigator Markku Laakso) - normoglycemia Exclusion Criteria: - type 2 diabetes - other chronic diseases Inclusion Criteria: - BMI >20kg/m2 <29kg/m2 - Pro12Pro and Ala12Ala genotypes of PPARG Pro12Ala polymorphism - participation to METSIM-study (METabolic Syndrome in Men, currently >10000 men included from the population living in Kuopio, principal investigator Markku Laakso) - normoglycemia Exclusion Criteria: - type 2 diabetes - other chronic diseases Insulin Sensitivity Hypersensitivity Insulin Resistance Obesity and type 2 diabetes are increasing in all western countries, including Finland. --- Pro12Ala ---

Inclusion Criteria: - BMI >20kg/m2 <29kg/m2 - Pro12Pro and Ala12Ala genotypes of PPARG Pro12Ala polymorphism - participation to METSIM-study (METabolic Syndrome in Men, currently >10000 men included from the population living in Kuopio, principal investigator Markku Laakso) - normoglycemia Exclusion Criteria: - type 2 diabetes - other chronic diseases Inclusion Criteria: - BMI >20kg/m2 <29kg/m2 - Pro12Pro and Ala12Ala genotypes of PPARG Pro12Ala polymorphism - participation to METSIM-study (METabolic Syndrome in Men, currently >10000 men included from the population living in Kuopio, principal investigator Markku Laakso) - normoglycemia Exclusion Criteria: - type 2 diabetes - other chronic diseases Insulin Sensitivity Hypersensitivity Insulin Resistance Obesity and type 2 diabetes are increasing in all western countries, including Finland. --- Pro12Ala --- --- Pro12Ala ---

The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. --- Pro12Ala ---

Based on these findings the investigators created in collaboration with Johan Auwerx an Pro12Ala animal model that demonstrated a differential effect of dietary fat composition depending on the genotype. --- Pro12Ala ---

However, an important conclusive proof that subjects selected based on their Pro12Ala genotype would respond differently to specifically tailored diet modification is still needed. --- Pro12Ala ---



HPO Nodes


HPO:
Allergy
Genes 13
CSTA ADA BBS1 CHD1 RBM8A TGM5 PGM3 PLCG2 SIK3 COX4I2 CARMIL2 SPINK5 FOXP3
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