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


HP:0000822: Hypertension
Genes 418
PDE11A WT1 BBS10 TGFB2 COL1A1 KCTD1 MLX ND5 SCNN1A GPR101 TRNS2 B2M CFI NOTCH3 ALX4 TNFRSF11A GATA5 EXT2 LYZ MUC1 ERCC6 TRNL1 STOX1 COX3 PRKACA MTTP BSCL2 TRNS1 PKD2 KRT8 TRNL1 SLC2A10 CDH23 LEMD3 WT1 TBX1 TRIM28 KCTD1 ND1 CYTB WNK1 ELP1 WDR19 AIP COX2 LOX TGFBR2 GCH1 KRT18 SCNN1B CORIN UFD1 CFH SCNN1G HGD PDE11A COL4A4 BRCA2 NR3C1 CACNA1D LMNA FBN1 ND1 TRNQ VHL JMJD1C CBS RPGRIP1L TGFBR3 POR SDHD TRNS1 ALMS1 CACNA1H TSC1 LRP6 CD2AP FBN1 COX2 DYRK1B SEC24C ADA2 HPSE2 NF1 LDLRAP1 HLA-DRB1 WNK4 ACVRL1 CCND1 FBN1 VHL GLA PDE3A ABCG8 SH2B3 MMP2 SLC52A2 ARMC5 SLC25A11 ERCC4 BBIP1 PAM16 HLA-DPA1 PDE8B ACAT1 LMNA GLA GUCY1A1 MAFB DIS3L2 COL5A2 NKX2-5 CYP11B1 TRNL1 BBS1 FGFR2 LEMD3 MYH7 PPARG FLT1 FN1 COMT MYMK MTRR FOXF1 FN1 CFB MKKS SDHD CYP11B1 MGP SDCCAG8 GJA1 SH2B3 CYP17A1 SUGCT TGFB3 COX1 ANGPTL6 ELN ACTN4 REST HMBS HSD11B2 ND5 SDHD SMAD4 ND4 KCNJ5 LRIG2 NPHP1 TRNQ FMO3 HMBS PTPN22 FGFR2 GBA ELN KIF1B SDHB SLC2A10 COX1 ENG RREB1 CCR6 CYP11B1 PLIN1 CCN2 LMX1B ACTA2 CD46 VHL CACNA1D G6PC PPARG MMP14 NPHP1 WRN APOA1 GP1BB KCNJ5 GPC3 ARHGAP31 RFC2 SMAD3 ND6 MAX SCNN1B ND6 CTLA4 PRTN3 SCNN1G RET PLIN1 USP8 C3 XYLT1 HLA-B XYLT2 FGA TRNC TRNF EPAS1 APOB BBS7 BBS2 BNC2 FOXE3 SDHC IQCB1 NOS3 BBS9 ABCC6 KIF1B COL4A5 H19 EDA2R CYP17A1 ELN PKHD1 HBB ENPP1 LIMK1 TBL2 LZTFL1 CPOX CEP164 USP8 CALR KIF1B SLC37A4 ZMPSTE24 TRNF SERPINA6 TMEM67 VHL JAK2 MDH2 ARMC5 SMARCAL1 FUZ ABCC6 TRNW POU3F4 SDHB NSMCE2 OFD1 MEF2A WT1 KLHL3 XPNPEP3 HIRA GNAS TP53 PDE3A CEP19 BANF1 SPRY2 INVS ADA2 BBS1 FBN1 NOD2 SDHC CLIP2 ERCC8 HSD11B2 NPHP3 TMEM127 HLA-DPB1 TNFRSF11B SDCCAG8 DLST MC4R CEP290 EGFR STAT1 TMEM127 COL3A1 YY1AP1 CAV1 COQ7 INVS ADA2 NOTCH1 TRNK BBS12 NFIX TRIP13 TRPC6 IDUA OFD1 LMX1B WDR35 ENPP1 BMPR2 CEP290 MFAP5 LMNA TRNK MKS1 POU6F2 PKD1 CC2D2A MAT2A MYH11 LDLR RET COL3A1 VHL CCDC28B SCN2B SDHB NOTCH2 ECE1 CDH23 IFT27 TRNV SMAD4 TRIM32 SDHAF2 GNAS MYLK ALMS1 ARL6 TSC2 AIP PRKAR1A WT1 ITGA8 TRIM28 ARVCF GTF2I LARS2 TRNW THPO COX3 CYP11B2 TMEM237 SLC37A4 CYP11B1 IFT172 COL5A1 SMAD6 TRAF3IP1 TMEM70 TRNH FH DNAJB11 NFU1 CFHR1 TBX1 BBS4 KCNJ5 COL4A3 AIP TRNS2 NR3C1 MLXIPL NPHP1 LMNA GUCY1A1 EDA SLC25A11 ACTA2 SCNN1A CFHR3 FMR1 LMNA TTC8 PRKG1 PRKACA TGFBR1 FIG4 ELP1 BAZ1B IL12B MAX IRF5 NPHP4 PHF21A ABCC6 RET WDPCP YY1AP1 CUL3 COL4A3 ADAMTSL4 BBS5 SLC52A3 OSGEP GANAB GNAS CYP21A2 TRNE SDHB ABCB6 VAC14 JAK2 RET SDHA PRKAR1A SDHD PCSK9 GDNF WT1 TET2 NR3C2 SMAD4 CLCN2 ABCG5 MPL C8ORF37 GTF2IRD1 VANGL1 TRNK THBD PRKAR1A