SNPMiner Trials by Shray Alag


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Report for SNP rs174537

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 3 clinical trials

Clinical Trials


1 Screening of Healthy Adults for Genetic Variations That Control Fatty Acid Processing

The purpose of this research study is to screen healthy African American and Caucasian persons for specific differences in genes that control how fats are processed in the body.

NCT01516125 Healthy

Determine the genotype at the rs174537 single-nucleotide polymorphism (SNP) in the fatty acid desaturate (FADS) gene cluster.

Primary Outcomes

Measure: Determine the genotype at the rs174537 single-nucleotide polymorphism (SNP) in the fatty acid desaturate (FADS) gene cluster

Time: up to 52 months

2 Fatty Acid Desaturase Activity, Fish Oil and Colorectal Cancer Prevention

Colorectal cancer is the second leading cause of cancer-related death within the United States. Animal models and observational studies have suggested that marine-derived n-3 polyunsaturated fatty acids [PUFA] such as eicosapentanoic acid [EPA] and docosahexanoic acid [DHA] may reduce the risk of colorectal cancer. In addition, it may be the relative proportion of n-3 to n-6 PUFAs that best determines the chemopreventive effects of fish oils. This ratio is important because the n-6 PUFA, arachidonic acid (ARA), is converted via the cyclo-oxygenase (COX) pathway to prostaglandin E2 (PGE2), an inflammatory eicosanoid overproduced in colorectal neoplasms while EPA is converted to the anti-inflammatory prostaglandin E3 (PGE3). While the ratio of n-6 to n-3 PUFAs can be altered through dietary changes, genetic factors may also influence this ratio. Recent genetic studies have demonstrated that much of the tissue levels of ARA is determined by differences in a gene called fatty acid desaturase 1 (FADS1). FADS1 is the rate-limiting enzyme in the conversion of linoleic acid, the most commonly consumed PUFA in the Western diet, to ARA, and one particular genetic variant caller rs174537 is associated with lower fatty acid desaturase activity and subsequently lower tissue levels of ARA. The study hypothesis is that individuals with genetically determined lower activity of FADS1 will derive greater benefit from fish oil supplementation than individuals with higher FADS1 activity because of lower tissue levels of ARA and subsequently a more favorable n-6 to n-3 PUFA ratio. To test this hypothesis the investigators will recruit 150 participants with recently identified adenomatous polyps and conduct a 6-month double blind 3 X 2 factorial randomized controlled trial. The first factor will be FADS1 genotype (GG, GT, and TT) and the second factor will be fish oil supplementation (fish oil versus placebo). The primary outcome will be the change in rectal epithelial cell growth and cell death. Secondary outcomes will include rectal epithelial cell expression of genes important in PGE2 production, rectal cell production of PGE2 and PGE3, rectal mucosal tissue levels of fatty acids, and changes in biomarkers of inflammation (C-reactive protein), adipokines (leptin, adiponectin), and markers of insulin sensitivity. The specific aims include: 1) to determine the efficacy of fish oil supplements on rectal epithelial cell proliferation indexes and markers of rectal crypt apoptosis, and 2) to determine the effect of genetically-determined fatty acid desaturase 1 activity on fish oil supplementation for colorectal cancer chemoprevention. The investigators long-term objectives are to determine genetic factors that might influence the efficacy of fish oil supplementation in order to conduct a more definitive adenoma recurrence trial using marine-derived n-3 PUFAs. The investigators anticipate that fish oil will have anti-neoplastic effect and individuals with low FADS1 activity will have a greater response compared to individuals with high FADS1 activity

NCT01661764 Co Colorectal Adenomatous Polyps Drug: Eicosapentanoic acid and docosahexanoic acid Drug: Oleic Acid
MeSH: Adenomatous Polyps

FADS1 is the rate-limiting enzyme in the conversion of linoleic acid, the most commonly consumed PUFA in the Western diet, to ARA, and one particular genetic variant caller rs174537 is associated with lower fatty acid desaturase activity and subsequently lower tissue levels of ARA.

FADS1 is the rate-limiting enzyme in the conversion of linoleic acid (LA), the most commonly consumed PUFA, to ARA, and homozygotes for the T allele (population frequency of 13%, HapMap -CEU) in rs174537 have lower fatty acid desaturase activity and subsequently lower tissue levels of ARA.

The first factor will be the rs174537 genotype (GG, GT, and TT) in the FADS1 gene and the second factor will be fish oil supplementation (fish oil versus placebo).

Primary Outcomes

Description: The primary outcome of interest is rectal epithelial cell proliferation, as measured by Ki67 (mib-1) labeling. Expression of Ki-67 in colon epithelial cells will be detected following the standard IHC protocol of EnVision™+ System, HRP (DAKO).

Measure: Rectal Epithelial Cell Proliferation

Time: 6 month

Description: The primary outcome of interest is rectal epithelial cell apoptosis as measured by TUNEL (TdT-mediated dUTP Nick-End Labeling). The TUNEL assay is conducted to measure apoptosis of colon epithelium using DeadEnd Colorimetric TUNEL System (Promega). After all fields of each sample are measured, the final immunoreaction indices are generated automatically by setting algorithms as ''total positive area / total nuclear area. Apoptotic activity is also scored using standard morphologic criteria applied to H&E stained sections.

Measure: Rectal Epithelial Cell Apoptosis

Time: 6 months

Secondary Outcomes

Description: Expression of COX-2 in rectal epithelial cells will be detected following the standard IHC protocol of EnVision™+ System, HRP (DAKO).

Measure: Rectal Epithelial Cell COX-2 Expression

Time: 6 months

Description: Expression of 15-PGDH in rectal epithelial cells will be detected following the standard IHC protocol of EnVision™+ System, HRP (DAKO).

Measure: Rectal Epithelial Cell 15-PGDH Expression

Time: 6 months

Description: Lipids will be extracted using the method of Folch-Lees

Measure: Rectal Epithelial Cell Phospholipid Fatty Acid Content

Time: 6 months

Description: liquid chromatography/tandem mass spectrometric on rectal biopsy samples

Measure: Rectal Epithelial Cell Production of PGE2 and PGE3

Time: 6 months

Other Outcomes

Measure: C-reactive Protein

Time: 6 months

Description: leptin and adiponectin

Measure: Adipokines

Time: 6 months

Description: homeostasis model assessment-insulin resistance (HOMA-IR) HOMA-IR. Fasting insulin and glucose were be used to determine HOMA-IR: [fasting glucose (mmol/l) x fasting insulin (µU/ml)]/22.5]", Optimal insulin sensitivity: < 1, Early insulin resistance: > 1.9, Significant insulin resistance: > 2.9

Measure: Insulin Sensitivity

Time: 6 months

3 Role of Fatty Acid Desaturase(s) (FADS) Polymorphisms in Determining the In Vivo Metabolism of Polyunsaturated Fatty Acids (PUFAs) in Botanical Oils in Humans.

A randomized, controlled, cross-over clinical trial of borage oil vs soybean oil to determine whether the metabolism and/or impact of medium chain-polyunsaturated fatty acids (MC-PUFAs) in botanical oil supplements are changed in relationship to specific genotypes in a SNP (rs174537) strongly associated with FADS1 activity and PUFA metabolism.

NCT02337231 Genetic Differences of Lipid Metabolism/Healthy Subjects Dietary Supplement: soybean oil and borage oil

Role of Fatty Acid Desaturase(s) (FADS) Polymorphisms in Determining the In Vivo Metabolism of Polyunsaturated Fatty Acids (PUFAs) in Botanical Oils in Humans.. Botanical Oils Study to Determine Genetic Differences in the Way Your Body Processes Fats in Edible Oils A randomized, controlled, cross-over clinical trial of borage oil vs soybean oil to determine whether the metabolism and/or impact of medium chain-polyunsaturated fatty acids (MC-PUFAs) in botanical oil supplements are changed in relationship to specific genotypes in a SNP (rs174537) strongly associated with FADS1 activity and PUFA metabolism.

Inclusion Criteria: - Able to give informed consent - Must agree to adhere to dietary requirements during the entire study - Be willing to participate for the whole study - Be willing to not take PUFA supplements outside of those provided by the study - Agree not to take interfering medications during the duration of the study - Agree to allow samples to be stored for future use Exclusion Criteria: - May not have diabetes, cancer, heart attack or vascular surgery within the past year, be diagnosed with heart disease, have uncontrolled high blood pressure, history of stroke, atherosclerosis, asthma, multiple sclerosis or chronic joint disease - Gallbladder removal or gallbladder disease - Use of tobacco products within the last six months - Pregnancy or lactation - Fasting triglycerides greater than 150 mg/dl - Blood pressure greater than 130/90 - BMI equal to or greater than 30 or less than 19 - Fasting glucose greater than 125 mg/dl - Have liver function values in the normal range - Taking greater than 100 mg aspirin/day - Taking NSAIDS or oral corticosteroids - Taking montelukast-type allergy medications - Having a pacemaker or a defibrillator - Taking lipid lowering medications Inclusion Criteria: - Able to give informed consent - Must agree to adhere to dietary requirements during the entire study - Be willing to participate for the whole study - Be willing to not take PUFA supplements outside of those provided by the study - Agree not to take interfering medications during the duration of the study - Agree to allow samples to be stored for future use Exclusion Criteria: - May not have diabetes, cancer, heart attack or vascular surgery within the past year, be diagnosed with heart disease, have uncontrolled high blood pressure, history of stroke, atherosclerosis, asthma, multiple sclerosis or chronic joint disease - Gallbladder removal or gallbladder disease - Use of tobacco products within the last six months - Pregnancy or lactation - Fasting triglycerides greater than 150 mg/dl - Blood pressure greater than 130/90 - BMI equal to or greater than 30 or less than 19 - Fasting glucose greater than 125 mg/dl - Have liver function values in the normal range - Taking greater than 100 mg aspirin/day - Taking NSAIDS or oral corticosteroids - Taking montelukast-type allergy medications - Having a pacemaker or a defibrillator - Taking lipid lowering medications Genetic Differences of Lipid Metabolism/Healthy Subjects The study will be a randomized, controlled, cross-over clinical trial of borage oil and soybean oil to determine whether the metabolism and/or impact of MC-PUFAs in botanical oil supplements are changed in relationship to specific genotypes in a SNP (rs174537) strongly associated with FADS1 activity and PUFA metabolism.

Subjects previously genotyped at rs174537 will be given supplements and both blood PUFA (serum and erythrocyte membranes), urinary eicosanoids and eicosanoid release from whole blood (leukocyte generation) will be measured as biochemical determinants of genotype impact on supplement metabolism.

To evaluate the effect of genotype at the rs174537 locus on the metabolism of MC-PUFAs in borage and soybean oil to long chain polyunsaturated fatty acids (LC-PUFAs), including arachidonic acid, the investigators will utilize a double blind, randomized, crossover design.

There will be three study groups based on the genotype of the healthy volunteer at rs174537.

Primary Outcomes

Measure: Change in serum fatty acids from baseline as measured in mass and recorded as mg/dL

Time: 16-week study


HPO Nodes