SNPMiner Trials by Shray Alag


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Report for SNP rs1801133

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 5 clinical trials

Clinical Trials


1 Pilot Evaluation of the Effect of Riboflavin Supplementation on Blood Pressure and Possible Effect Modification by the MTHFR C677T Genotype

Hypertension, which results from a combination of multiple lifestyle and genetic factors, is a global public health problem affecting 1 billion people worldwide. The identification of cheap treatment interventions without adverse side effects would be hugely advantageous particularly in low-income settings with high prevalence of hypertension such as sub-Saharan Africa where up to 46% of adults are affected. Emerging evidence links a functional polymorphism in the MTHFR gene (rs1801133 C677T), encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase to high blood pressure in adults. Variation at rs1801133 is relatively common and has 3 genotypes; homozygous "normal" CC, heterozygous CT and homozygous "variant" TT genotypes. Of these genotypes, the homozygous "variant" TT is more strongly associated with a higher BP. The precise mechanism by which MTHFR is associated with BP remains unclear. It has been recently shown in 3 separate randomized controlled trials that BP is highly responsive to riboflavin and that this response is differential by MTHFR rs1801133 genotype. In all these clinical trials, significant reduction in both systolic and diastolic blood pressure was observed in the homozygous variant TT genotype and an intermediate effect seen in those with the heterozygous CT genotype. The aim of this study is to evaluate the effect of riboflavin supplementation on blood pressure in a riboflavin-deplete population as well as comparing plasma riboflavin status before and after supplementation. This will be achieved by conducting a randomized single-blind placebo controlled trial over a period of 16 weeks. The Investigators will use the Keneba biobank to invite about 100 adults with the CT genotype and a similar number of age-, sex and village-matched CC homozygotes. Participants within each of the groups will be randomized to receive either riboflavin (5mg/d) or a matching placebo which would be supplied on a weekly basis. Blood sample, blood pressure measurement, socio-demographic data and their anthropometric measurements (height, weight, waist and hip circumference and body composition by BIA) will be taken during the initial visit. An additional blood sample will be taken at the end of the study whilst additional BP measurements will be taken respectively at 8 weeks and at the end of the intervention. The possibility that riboflavin deficiency represents a new, easily-correctible causal factor in hypertension in sub-Saharan Africa would require further large-scale interventions if this pilot study yields encouraging results.

NCT03151096 High Blood Pressure MTHFR C677T Genotype Dietary Supplement: Riboflavin Dietary Supplement: Placebo
MeSH: Hypertension
HPO: Hypertension

Emerging evidence links a functional polymorphism in the MTHFR gene (rs1801133 C677T), encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase to high blood pressure in adults.

Variation at rs1801133 is relatively common and has 3 genotypes; homozygous "normal" CC, heterozygous CT and homozygous "variant" TT genotypes.

It has been recently shown in 3 separate randomized controlled trials that BP is highly responsive to riboflavin and that this response is differential by MTHFR rs1801133 genotype.

We would like to investigate if there is any effect modification in CC vs CT variants of rs1801133 in the MTHFR gene in response to riboflavin supplementation vs placebo.

Primary Outcomes

Description: The aim of this study is to investigate whether supplementing 5mg of riboflavin can decrease blood pressure more effectively compared with placebo

Measure: Blood Pressure

Time: 16 weeks

Description: We will compare EGRAC in those who were randomised to riboflavin supplementation versus placebo

Measure: Erythrocyte Glutathione Reductase Activation Coefficient (indicator of riboflavin status)

Time: 16 weeks

Secondary Outcomes

Description: We would like to investigate if there is any effect modification in CC vs CT variants of rs1801133 in the MTHFR gene in response to riboflavin supplementation vs placebo

Measure: Blood pressure

Time: 16 weeks

Description: We aim to describe the cross-sectional associations at baseline between blood pressure (continuous variable and proportion >140/90mm) and riboflavin status (assessed by the Erythrocyte Glutathione Reductase Activation Coefficient) and MTHFR variants

Measure: Blood pressure and plasma riboflavin status

Time: 16 weeks

2 The Effect of Betaine Supplementation on Body Composition and Physical Capacity of Speed-strength Male Athletes

The study is aimed at assessing the influence of two betaine doses (2.5 g∙d-1 and 5 g∙d-1) supplemented for three weeks in a group of speed-strength trained athletes on anaerobic capacity in Wingate test, performance in CrossFit-like exercise test - Fight Gone Bad, alterations in body compositions and total body water.

NCT03702205 Supplementation Sport Dietary Supplement: Betaine supplementation Dietary Supplement: Placebo treatment

Difference in response to betaine supplementation depending on MTHFR (rs1801133) polymorphism.

MTHFR (rs1801133) polymorphism.

Primary Outcomes

Description: Fat mass (kg) and fat free mass (kg) analysis

Measure: Changes in fat mass and fat free mass after betaine supplementation

Time: Baseline and after 3 weeks

Description: The Wingate cycling test (W)

Measure: Changes in anaerobic capacity after betaine supplementation

Time: Baseline and after 3 weeks

Description: The CrossFit-specific physical fitness test: Fight Gone Bad (reps.)

Measure: Changes in specific performance capacity after betaine supplementation

Time: Baseline and after 3 weeks

Secondary Outcomes

Description: Total body water content (%)

Measure: Changes in total body water after betaine supplementation

Time: Baseline and after 3 weeks

Description: Testosterone level (ng/L)

Measure: Changes in testosterone level (ng/L) after betaine supplementation

Time: Baseline and after 3 weeks

Description: Amino acid profile (μmol/L)

Measure: Changes in amino acid profile after betaine supplementation

Time: Baseline and after 3 weeks

Description: Blood betaine (µmol/L)

Measure: Changes in blood betaine

Time: Baseline and after 3 weeks

Description: Total, LDL and HDL cholesterol (mg/dL) and triacylglycerol (mg/dL)

Measure: Changes in total, LDL and HDL cholesterol and triacylglycerol after betaine supplementation

Time: Baseline and after 3 weeks

Description: MTHFR (rs1801133) polymorphism

Measure: Difference in response to betaine supplementation depending on MTHFR (rs1801133) polymorphism

Time: Baseline and after 3 weeks

3 Association of the C677T and A1298C MTHFR Polymorphisms With Chemotherapy Effectiveness Among Patients With Metastatic Colorectal Cancer

Fluoropyrimidines are the backbone of chemotherapy regimes used to treat metastatic colorectal cancer (CRC). These drugs act in different pathways of folate metabolism altering DNA synthesis mainly by inhibition of the tymidylate synthase. For this reaction the 5,10-methylenetetrahydrofolate acts as cofactor. It has been demonstrated that A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene result in reduced enzyme activity that leads to reduced availability of this important cofactor. Hence, we hypothesized that the presence of these polymorphisms are related to the efficacy and toxicity of fluoropyrimidines in patients with CRC.

NCT03852290 Colon Cancer MTHFR Gene Mutation Chemotherapeutic Toxicity Chemotherapy Effect
MeSH: Colonic Neoplasms
HPO: Colon cancer Neoplasm of the colon

DNA extraction will be done from blood and tissue samples to determine the C677T (rs1801133) and 1298 A>C (rs18011131) polymorphisms of the MTHFR gene.

Primary Outcomes

Description: Overall survival

Measure: Assessment of C677T and A1298C MTHFR polymorphisms and overall survival

Time: From the start date of treatment until the date of death from any cause, assessed up to 24 months

Description: Progression-Free survival

Measure: Assessment of C677T and A1298C MTHFR polymorphisms and progression-free survival

Time: From the start date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Description: Response rate

Measure: Assessment of C677T and A1298C MTHFR polymorphisms and response rate

Time: From the start date of treatment until the first radiological or clinical assessment, up to 6 months.

Secondary Outcomes

Description: Prospective assessment of toxicity according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) 4.0 criteria according to the C677T and A1298C polymorphisms

Measure: Assessment of C677T and A1298 MTHFR polymorphisms and toxicity

Time: From treatment initiation to detected toxicity during treatment with any fluoropyrimidine alone or in combination with oxaliplatin, irinotecan or any biological treatment as first line therapy of colorectal metastatic cancer (up to 24 months)

4 Is Natural Folate as Effective as Synthetic Folic Acid in Increasing Serum and Red Blood Cell Folate Concentrations During Pregnancy? A Proof-of-concept Pilot Study

In this two-arm, double-blind randomized pilot study, the investigators will recruit 60 generally healthy, low-risk pregnant women aged 19-42 years living in Vancouver, Canada. Participants will be randomized to supplement with either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16-weeks of their pregnancy. Randomization will occur at 8-21 weeks gestation (after neural tube closure) to reduce the risk of harm should the natural folate prove less effective. All participants will also receive a prenatal multivitamin not containing any form of folate, to ensure adequacy of other nutrients (e.g. iron) required during pregnancy. Three-hour fasting venous blood samples will be collected at baseline and endline to measure serum and red blood cell folate, unmetabolized folic acid and other related biomarkers. Women will be given the option to continue supplementing until 1-week postpartum, and provide a small (3mL) breastmilk sample in order to measure differences in folates in breastmilk. These pilot data will be used to inform a definitive trial regarding the most effective form of folate supplementation for mothers and their babies.

NCT04022135 Pregnancy Dietary Supplement: Folic acid Dietary Supplement: (6S)-5-methyltetrahydrofolic acid

Gene variant assessment of MTHFR (677 C>T, rs1801133, and 1298 A>C, rs1801131) and DHFR (rs1643649 and rs70991108) and differences in DNA methylation.

Primary Outcomes

Description: nmol/L; Reflects longer term status (e.g. previous 3-4 months)

Measure: Concentration of red blood cell folate levels

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: nmol/L; Reflects recent status or dietary intake

Measure: Concentration of serum folate levels

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: nmol/L; unmetabolized folic acid is not incorporated into RBCs, rather it circulates in plasma

Measure: Concentration of unmetabolized folic acid

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Secondary Outcomes

Description: pmol/mL; closely involved in folate metabolism and facilitating methionine cycles

Measure: Concentration of total vitamin B-12

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: nmol/L; closely involved in folate metabolism and facilitating methionine cycles

Measure: Concentration of pyridoxal-5'-phosphate

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: µmol/L; closely involved in facilitating methionine cycles

Measure: Concentration of betaine

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: µmol/L; closely involved in facilitating methionine cycles

Measure: Concentration of choline

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: µM; Metabolite produced in methionine cycles

Measure: Concentration of S-adenosyl-methionine

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: µM; Metabolite produced in methionine cycles

Measure: Concentration of S-adenosyl-homocysteine

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: µmol/L; Metabolite produced in methionine cycles

Measure: Concentration of total homocysteine

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: µmol/L; Metabolite produced in methionine cycles

Measure: Concentration of methionine

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: µmol/L; Metabolite produced in methionine cycles

Measure: Concentration of cysteine

Time: concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation), and calculation of change between time periods

Description: Gene variant assessment of MTHFR (677 C>T, rs1801133, and 1298 A>C, rs1801131) and DHFR (rs1643649 and rs70991108) and differences in DNA methylation

Measure: Collection of peripheral blood mononuclear layer cells

Time: Collection at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation)

Description: nmol/L; folic acid that is unmetabolized and enters breastmilk as such

Measure: Concentration of unmetabolized folic acid in breastmilk

Time: Collection at 1 week postpartum

Description: nmol folate binding per liter of milk

Measure: Folate binding protein in breastmilk

Time: Collection at 1 week postpartum

5 A Retrospective Cohort Study: The Influence of MTHFR C677T and A1298C on the High-dose Methotrexate-Related Toxicities in Pediatric Patients With Non-Hodgkin Lymphoma

We hypothesized that polymorphism MTHFR C677T and A1298C should be associated with HD-MTX-related toxicities in children with NHL. Therefore, we aimed to retrospectively explore their relationships in this analysis.

NCT04283955 Pediatric NHL Drug: High-dose MTX based chemotherapy
MeSH: Lymphoma, Non-Hodgkin
HPO: Non-Hodgkin lymphoma

The most two extensively studied SNPs of MTHFR in relation to the toxicities of MTX are the C677T variant (Ala222Val, rs1801133) and A1298C variant (Glu 429Ala, rs1801131), both dampening the enzyme activity by 40-70%.

Primary Outcomes

Description: We recorded the toxicities that occurred to the patients after the MTX infusion, including hematological suppression, hepatotoxicity, nephrotoxicity, oral mucositis, vomiting and diarrhea.

Measure: Observations of HD-MTX-related toxicities

Time: 3 weeks


HPO Nodes


Colon cancer
Genes 59
TP53 TRIP13 COL14A1 SMAD4 BRCA2 MLH1 MSH6 HABP2 PMS2 APC BUB1B PALLD BUB1 GREM1 NTHL1 PMS1 MSH6 AXIN2 APC EPCAM BUB3 MSH2 APC KRAS TGFBR2 FAN1 MINPP1 APC MSH3 SH3KBP1 TP53 KRAS AAGAB SMAD4 BMPR1A MSH2 BMPR1A MLH3 MSH2 PALB2 MUTYH FLCN PIK3CA BMPR1A FOXE1 MSH2 SMAD7 MLH1 CEP57 MLH1 BRCA1 RPS19 PRKAR1A PMS1 APC CDKN2A APC MLH1 APC
Non-Hodgkin lymphoma
Genes 32
ATM FAS CASP10 CTLA4 FAS BCL10 CD28 BIRC3 FOXP1 TNFRSF1B MYC CCND1 ASXL1 ATM MALT1 CTLA4 CD28 SRSF2 KIT POLE IGH ADA TET2 FASLG PIK3R1 NTHL1 RASGRP1 TNFRSF1B PRKCD NBN RHOH IGH
Hypertension
Genes 410
GPC3 MPL PRKAR1A ABCG8 ND1 CYP11B1 TRNS1 B2M MMP2 BRCA2 SDCCAG8 HMBS LYZ PKD1 C8ORF37 BSCL2 WT1 SCNN1B SLC25A11 COX2 CEP19 TRNQ YY1AP1 ECE1 WT1 KCNJ5 ENPP1 FN1 PDE11A HGD SLC25A11 HSD11B2 MFAP5 GUCY1A1 DYRK1B SPRY2 SLC2A10 SMAD6 COX3 SCNN1G SCNN1B LARS2 FOXF1 NPHP4 TRNL1 TMEM67 IL12B HIRA TRIM28 MLXIPL CDH23 CLIP2 HLA-B TRNF POU6F2 NFU1 SDHC CEP290 ENPP1 EDA CYTB SDCCAG8 HLA-DPB1 SCNN1A NKX2-5 COL5A1 LEMD3 YY1AP1 TBL2 ALMS1 NOTCH3 CLCN2 ARVCF SEC24C CFH FH TGFB2 TMEM127 ARMC5 AIP SDHA JMJD1C COX1 ND5 COMT NF1 CACNA1D TGFBR1 REST LDLRAP1 GTF2I PDE3A TNFRSF11B MAT2A HSD11B2 TRNH CORIN SERPINA6 BBS10 AIP MAFB FOXE3 SCN2B SMAD4 CYP11B1 TRNK SLC52A3 TRNL1 CYP17A1 GBA SDHB BBS1 HBB CCR6 XPNPEP3 ERCC4 VHL BBS7 GP1BB TRNE OSGEP PPARG NOS3 TRPC6 HMBS JAK2 VHL KRT18 TRNS1 WT1 NPHP1 SDHD INVS KCTD1 OFD1 USP8 FIG4 TRIM28 LRIG2 PCSK9 SDHB SCNN1G CCN2 COL1A1 TRNL1 WT1 PTPN22 LDLR PRKAR1A COX1 VHL TRNC COQ7 LEMD3 PRKACA MKKS BBS5 SLC52A2 SDHD TRNW COX3 RREB1 GPR101 SMAD3 INVS KIF1B DNAJB11 COX2 APOA1 RET ARHGAP31 KCNJ5 WT1 ND5 GDNF CUL3 GLA FLT1 ACVRL1 TNFRSF11A VHL GNAS PRTN3 COL3A1 ABCC6 XYLT1 CYP11B1 ADAMTSL4 FGA C3 COL5A2 BBS9 ERCC6 KCNJ5 FBN1 APOB BAZ1B PAM16 POU3F4 TMEM70 ND4 STOX1 GNAS RFC2 TGFBR2 CALR IQCB1 CYP21A2 MMP14 SLC37A4 ALX4 TRNQ TBX1 THPO GTF2IRD1 GATA5 ND6 FN1 RPGRIP1L CFB ANGPTL6 RET XYLT2 VANGL1 NR3C1 PDE11A NR3C2 POR TRNK BMPR2 MGP TRNV SUGCT RET MYH11 PRKAR1A MDH2 FMO3 KLHL3 WNK4 TMEM237 LZTFL1 TRNK IRF5 STAT1 NSMCE2 MUC1 COL4A4 HLA-DPA1 GLA IDUA NOTCH2 TRNW CC2D2A SCNN1A NR3C1 CPOX USP8 BBS2 ELN CYP11B2 SMARCAL1 LMX1B BNC2 TRIM32 MAX MKS1 PKD2 LRP6 PRKACA COL3A1 SDHD NPHP1 MAX PRKG1 MYLK HLA-DRB1 DIS3L2 CFI LMX1B ACAT1 ELN EGFR ND6 ELP1 ELN SLC37A4 PPARG CEP164 LMNA PLIN1 DLST TP53 TRNF SMAD4 LOX UFD1 FMR1 SDHB NOTCH1 SMAD4 BBS12 IFT172 ABCG5 MYMK CFHR1 TRIP13 SLC2A10 GJA1 WDPCP FUZ CYP17A1 TRNS2 WDR35 MYH7 SDHAF2 LMNA NPHP3 GUCY1A1 EXT2 HPSE2 OFD1 LMNA FGFR2 MEF2A PLIN1 COL4A3 CEP290 ACTA2 KIF1B CD2AP TGFB3 FBN1 TRNS2 SH2B3 COL4A5 NOD2 SDHC PDE3A G6PC THBD FBN1 CAV1 TTC8 ALMS1 ITGA8 LMNA GANAB LIMK1 BBIP1 CTLA4 BANF1 CCDC28B CFHR3 FBN1 H19 CACNA1H ARMC5 AIP CCND1 ADA2 ARL6 EDA2R CBS SH2B3 TET2 CACNA1D ADA2 ND1 VAC14 IFT27 PDE8B CYP11B1 TRAF3IP1 CDH23 BBS1 TMEM127 COL4A3 GNAS ELP1 ACTA2 NPHP1 MTTP WNK1 WDR19 ZMPSTE24 CD46 GCH1 KCTD1 ADA2 ABCB6 ACTN4 NFIX ENG TGFBR3 ABCC6 WRN LMNA BBS4 PKHD1 FGFR2 MC4R ERCC8 KIF1B KRT8 TBX1 JAK2 PHF21A MLX ABCC6