SNPMiner Trials by Shray Alag

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SNPMiner SNPMiner Trials (Home Page)


Report for SNP rs1544410

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 4 clinical trials

Clinical Trials


1 Vitamin D Supplementation Enhances Immune Response to BCG Vaccination in Infants

The purpose of this study is to determine whether a single oral dose of vitamin D given to infants prior to Bacille-Calmette-Guerin (BCG) vaccination will enhance the immune response to BCG vaccination.

NCT01288950
Conditions
  1. Tuberculosis
Interventions
  1. Dietary Supplement: Vitamin D3 (cholecalciferol)
MeSH:Tuberculosis

The investigators will also determine whether specific host genetic variants including the Fok-I(rs2228570T/C), Bsm-I(rs1544410A/G), GC(rs2282679A/C), DHCR7(rs12785878G/T) and CYP2R1 (rs10741657A/G) polymorphisms affect baseline vitamin D levels and alter the response to vitamin D supplementation.. Bacille-Calmette-Guerin (BCG) vaccine efficacy.

The investigators will determine whether specific host genetic variants including the Fok-I(rs2228570T/C), Bsm-I(rs1544410A/G), GC(rs2282679A/C), DHCR7(rs12785878G/T) and CYP2R1 (rs10741657A/G) polymorphisms affect the response to BCG vaccine in infants receiving either vitamin D or placebo.. Inclusion Criteria: - Healthy mothers > 18 years of age - Term, healthy infants eligible to receive the Bacille-Calmette- Guerin (BCG) vaccine Exclusion Criteria: - Recent maternal history of tuberculosis (within 1 year) or active tuberculosis - Known maternal human immuno-deficiency virus (HIV) infection - Maternal fever or chorio-amnionitis - Maternal use of vitamin D, steroids or immuno-regulatory medications - Household member with active tuberculosis Inclusion Criteria: - Healthy mothers > 18 years of age - Term, healthy infants eligible to receive the Bacille-Calmette- Guerin (BCG) vaccine Exclusion Criteria: - Recent maternal history of tuberculosis (within 1 year) or active tuberculosis - Known maternal human immuno-deficiency virus (HIV) infection - Maternal fever or chorio-amnionitis - Maternal use of vitamin D, steroids or immuno-regulatory medications - Household member with active tuberculosis Tuberculosis Tuberculosis In 2000, there were an estimated 884,000 cases of tuberculosis (TB) in children with many developing severe, disseminated disease.

Primary Outcomes

Description: BCG vaccine efficacy will be assessed by measuring the host immune response against BCG at 2 months, 6 months and one year after BCG immunization. A whole blood assay will be used to measure multiple cytokines and mycobacterial growth suppression.

Measure: Bacille-Calmette-Guerin (BCG) vaccine efficacy

Time: 2 months

Measure: Bacille-Calmette-Guerin (BCG) vaccine efficacy

Time: 6 months

Measure: Bacille-Calmette-Guerin (BCG) vaccine efficacy

Time: 1 year

Secondary Outcomes

Description: Serum 25 hydroxy (OH) vitamin D levels will be measured prior to vitamin D supplementation and at 2 months, 6 months and one year after BCG immunization. The investigators will also determine whether specific host genetic variants including the Fok-I(rs2228570T/C), Bsm-I(rs1544410A/G), GC(rs2282679A/C), DHCR7(rs12785878G/T) and CYP2R1 (rs10741657A/G) polymorphisms affect baseline vitamin D levels and alter the response to vitamin D supplementation.

Measure: Effect of a single dose of 50,000 IU vitamin D3 on serum vitamin D levels

Time: 2 months

Description: The investigators will determine whether specific host genetic variants including the Fok-I(rs2228570T/C), Bsm-I(rs1544410A/G), GC(rs2282679A/C), DHCR7(rs12785878G/T) and CYP2R1 (rs10741657A/G) polymorphisms affect the response to BCG vaccine in infants receiving either vitamin D or placebo.

Measure: Bacille-Calmette-Guerin (BCG) vaccine efficacy

Time: 1 year

2 Vitamin D Receptor and Megalin Gene Polymorphisms and Their Association With Obesity, Central Obesity and the Metabolic Syndrome

The link between metabolic disturbances and vitamin D receptor (VDR) and MEGALIN (or LRP2) gene polymorphisms remains unclear, particularly among African-American adults. The associations of single nucleotide polymorphisms (SNPs) for VDR [rs1544410(BsmI:G/A), rs7975232(ApaI:A/C), rs731236(TaqI:G/A)] and MEGALIN [rs3755166:G/A,rs2075252:C/T, rs2228171:C/T] genes with incident and prevalent metabolic disturbances, including obesity, central obesity and metabolic syndrome (MetS) were evaluated. From 1,024 African-Americans participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS, Baltimore, MD, 2004-2013) study, 539 subjects were selected who had complete genetic data as well as covariates selected for metabolic outcomes at two consecutive examinations (visits 1 and 2) with a mean follow-up time of 4.64±0.93y. Haplotype (HAP) analyses generated polymorphism groups that were linked to incident and prevalent metabolic disturbances.

NCT03279432
Conditions
  1. Metabolic Syndrome
  2. Obesity
  3. Central Obesity
MeSH:Obesity Metabolic Syndrome Obesity, Abdominal Syndrome
HPO:Abdominal obesity Obesity Truncal obesity

The associations of single nucleotide polymorphisms (SNPs) for VDR [rs1544410(BsmI:G/A), rs7975232(ApaI:A/C), rs731236(TaqI:G/A)] and MEGALIN [rs3755166:G/A,rs2075252:C/T, rs2228171:C/T] genes with incident and prevalent metabolic disturbances, including obesity, central obesity and metabolic syndrome (MetS) were evaluated.

Primary Outcomes

Description: Obesity was defined as BMI≥30 kg/m2.

Measure: Obesity

Time: 2004-2013

Description: Central obesity was defined based on waist circumference (WC) ≥ 102 cm or 40 inches (men), ≥ 88 cm or 35 inches (women)

Measure: Central Obesity

Time: 2004-2013

Description: Participants who screened positive on at least 3 of 5 conditions ((1) central obesity (see above); (2) dyslipidemia: TAG≥1.695 mmol/L (150 mg/dl); (3) dyslipidemia: HDL-C<40 mg/dL (male), <50 mg/dL (female); (4) blood pressure≥130/85 mmHg; (5) fasting plasma glucose≥6.1 mmol/L (110 mg/dl).(39)) were classified as MetS-positive (2) Similarly, continuous annual rates of change (Δ) in metabolic outcomes were considered, specifically number of metabolic disturbances (MetD), BMI, WC, SBP, DBP, TAG, HDL-C, and Glucose. Binary incident outcomes included obesity, central obesity, MetS and other metabolic disturbance (i.e. hypertension, dyslipidemia-TAG, dyslipidemia-HDL and hyperglycemia).

Measure: Metabolic Syndrome

Time: 2004-2013

3 Vitamin D and Skin Pigmentation in Healthy Humans Exposed to UVB

Skin pigmentation (melanin) absorbs ultra violet type B (UVB) radiation found in sunlight and is believed to be responsible for darker-skinned persons' generally low 25(OH)D status. This phenomenon is found in immigrants living in Northern countries and their 25(OH)D responses to UVB-irradiation seem low. We hypothesized that objectively measured skin pigmentation and/or pigment genes influence UVB-induced 25(OH)D increase significantly in combination with other influential parameters. The influence of objectively measured constitutive and facultative skin pigmentation on UVB-induced 25(OH)D increase over time was investigated together with other possible influential parameters. These other influential parameters include sex, age, weight, height, BMI, number of fatty fish meals per week, Fitzpatrick Skin Type and 25(OH)D start level. The genetic parameters include 33 Vitamin D receptor and pigment SNPs. This is a single-centre, open and non-blinded clinical trial. No randomisation was used, as the participants were allocated into two groups based on their Fitzpatrick Skin type and ethnic origin. The light-skinned group included participants with Fitzpatrick Skin type II-IV and were of Northern origin (Denmark, the Faroe Islands and the UK). The darker-skinned included Fitzpatrick Skin Types V-VI originating from countries located at latitudes below 50 degrees N. Thus, it could be ensured that the participants represented a wide range of skin pigmentation. The light-skinned (N = 22) and the darker-skinned subjects (N = 18) were exposed to identical UVB doses on identical body areas over nine weeks with weekly measurements of 25(OH)D. The UVB-induced 25(OH)D synthesis was investigated in summer-pigmented skin with melanin throughout the epidermis and during winter when ambient UVB exposure is negligible. Demographic data (gender, age, weight, height, Fitzpatrick Skin Type, measured constitutive and facultative skin pigmentation (PPF)) was collected/measured and registered in prior to study start. The number of daily consumed fatty fish meals was recorded in a questionnaire. Serum 25(OH)D was analysed weekly.

NCT03409510
Conditions
  1. Healthy Volunteers
Interventions
  1. Radiation: UVB radiation

The influence of the vitamin D receptor gene was investigated by genotyping the two single nucleotide polymorphisms (SNP), rs1544410 (BsmI) and rs2228570 (FokI), located in the gene (ENSG00000111424, Chromosome 12q13) as previously described.

Primary Outcomes

Description: Serum 25(OH)D is a marker of vitamin D increase induced by UVB

Measure: Change in serum 25(OH)D

Time: Measured at study start and weekly over nine weeks

4 Personalization of AntiTB Treatment: Evaluation of Pharmacological Determinants of Treatment Response

The aim of the study is to investigate the possible correlation of plasma drug concentrations with Time To Positivity (TTP) in liquid culture in patients with active pulmonary multi sensitive TB in the first two weeks of treatment. Secondary aims are: the correlation between plasma drug concentrations and hepato/neuro toxicity; the impact of different allelic variants on PK data, toxicity and TTP in liquid culture; the feasibility of using dried blood/plasma spots to measure plasma concentrations of anti-TB drugs and determine genetic polymorphisms.

NCT03416309
Conditions
  1. Tuberculosis, Pulmonary
MeSH:Tuberculosis Tuberculosis, Pulmonary

Analyzed SNPs will be: ABCB1 3435C>T (rs1045642), OATP1B1 521T>C (rs4149056) e OATP1B1 85-7793T>C (rs4149032), PXR 63396C>T (rs2472677), BsmI G>A (rs1544410).

Primary Outcomes

Description: Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with the change in Time To Positivity (TTP) in liquid culture in patients with active pulmonary TB between the baseline and the first week of treatment.

Measure: Correlation between AUC of RHZE and TTP

Time: 1 week from start of treatment

Description: Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with the change in Time To Positivity (TTP) in liquid culture in patients with active pulmonary TB between the baseline and the second week of treatment.

Measure: Correlation between AUC of RHZE and TTP

Time: 2 weeks from start of treatment

Secondary Outcomes

Description: Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with hepatotoxicity (increase of AST and/or ALT) and neurotoxicity (peripheral neuropathy)

Measure: Correlation between AUC of RHZE and toxicity

Time: 1 week and 2 weeks from start of treatment

Description: Investigate the impact of different allelic variants of NAT2, SLCO1B1, ABCB1, VDR on AUC of RHZE toxicity and TTP in liquid culture

Measure: Correlation between PG and AUC of RHZE

Time: 1 week and 2 weeks from start of treatment

Description: Assess the consistency of using dried plasma spots to measure plasma concentrations of anti-TB drugs comparing to plasma samples

Measure: Assess the consistency of results using of DPS for measuring the plasma drug concentrations

Time: 1 week and 2 weeks from start of treatment

Description: A pharmacometric model will be develop to correlate pharmacokinetics (AUC of RHZE) with the anti-TB treatment response (clinical and TTP) of the standard first-line anti-TB regimen.

Measure: Correlate AUC of RHZE with antiTB response

Time: 6 months after end of treatment

Description: A pharmacometric model will be develop to correlate PG with the anti-TB treatment response (clinical and TTP) of the standard first-line anti-TB regimen.

Measure: Correlate PG with antiTB response

Time: 6 months after end of treatment


HPO Nodes


HP:0001513: Obesity
Genes 522
NTRK2 BLK MERTK SH2B1 PROK2 MAGEL2 FEZF1 MEGF8 ALG13 CUL4B MAGEL2 BBIP1 AGTR2 ZNF711 GTF2IRD1 SLC9A7 SLC7A14 RP1 OFD1 CEP164 PHF21A FRMPD4 BRAF RTL1 PHF6 BBS1 FGFR3 CNNM2 GNAS PDE6A CNGB1 ARVCF HACE1 LIPE ZNF408 HNF4A WDR11 CTNNB1 EIF2S3 RREB1 TOPORS IFT172 OCA2 IFT172 LZTFL1 RBP3 ERMARD ARX SAG TMEM43 PAX4 ATP10A CEP290 UBE3A NDN NDN SYNE1 BBS10 H6PD DMD RAB39B FLRT3 PROKR2 RTL1 PCNT SIM1 TTC8 CLIP2 ABCC8 ELN TBX3 IGF1R HIRA GP1BB GNAS VPS13B OFD1 BAP1 EMD ADNP SEC24C ELN KLF11 TULP1 KIDINS220 GNAS KIF7 RNPC3 GHR SNRNP200 CLCN4 P4HTM AKT2 PRMT7 IFT74 GDI1 NEUROD1 SIN3A RTL1 HESX1 PTCHD1 C8ORF37 PDE4D WNT4 CREBBP NPAP1 PDE4D VPS13B SDC3 BBS4 SLC7A7 ARL6 RP9 IFT88 TMEM67 SLC10A7 RHO MYT1L BLM PDX1 NPHP1 ARL3 IFT27 RPGR FGFR1 PDE6B DLK1 ATP6AP2 MEG3 MC3R ZNF365 SNORD115-1 ZNF513 SRY BBS10 SOX3 SPRY4 RLBP1 RAB23 MKRN3-AS1 TSPAN7 ACADVL PDSS1 FAM161A FTSJ1 ROM1 PCSK1 SNRPN TTC8 FGF17 MAPK8IP3 SH2B1 IGF1 ZNF81 HUWE1 IDH3B BBIP1 PDE4D USP8 CACNA1S EGF FHL1 USP8 BEST1 KMT2A GNAS PWRN1 TBX3 IPW RP2 WDPCP KMT2D XYLT1 BBS9 ARNT2 APPL1 SUFU FGF8 PAK3 IMPDH1 SNRPN MEGF8 DHDDS EIF2S3 BAP1 GCK RAI1 MCM3AP SH2B1 RPE65 SNRPN ZBTB20 SMARCB1 NKAP SPATA7 HDAC8 P2RY11 WT1 XRCC4 PRMT7 ARHGEF18 BBS9 POMC HLA-DQB1 HS6ST1 TRIM32 WT1 CREBBP CANT1 OCA2 NR0B2 THOC2 LMNA KLHL7 STX16 SDCCAG8 RAD21 ALMS1 SEMA4A USH2A CERKL FMR1 TRAF7 CYP19A1 PAX6 TNFSF4 PTEN FGFR1 BBS7 DDX6 AFF4 MAGEL2 ACSL4 CHD7 CCDC141 PCNT PRPF8 MID2 GABRA3 BBS7 HNF1A KDM6A CDHR1 SNRPN HLA-DRB1 DYNC2I2 UBE3A TRIM32 MAGEL2 PWAR1 TRIP12 KCNJ11 EYS SYNE2 ARL6 SHOX TACR3 CNKSR2 CEP19 CLRN1 NIPBL SMAD4 NDN MTTP TCF20 USP9X MKRN3 ADRB3 SETD2 OCA2 MRAP2 ENPP1 DHX38 IFT172 ADRB2 CARTPT CUL4B SMO SNRPN DLK1 LEP CYP7A1 ARL2BP MAN1B1 PRCD IL1RAPL1 PRPH2 CDH23 NEK2 NSMF NDN REEP6 JMJD1C CREBBP AGBL5 PDGFB PROM1 TBX1 MTFMT MECP2 MAN1B1 GNAS LEPR TBL2 POMC SIM1 TBX1 BBS2 PIGT SDCCAG8 SPG11 EHMT1 IFT140 PNKP PSMD12 RFC2 GATA4 SNORD116-1 LEPR MKKS LMNA LIMK1 BLK MED12 BBS12 MKS1 PCSK1 SMARCE1 ABCA4 IDH3A EP300 BBS1 KIZ ATRX BBS5 BDNF TRAPPC9 IMPG2 HESX1 MKS1 PDE11A SIN3A SOX10 MAGEL2 SYP RPS6KA3 TBX1 ZNF41 KISS1R MEG3 STEEP1 IQSEC2 TRAF3IP1 TUB TAF1 ATRX PRDM16 UBE3A C8ORF37 DEAF1 LEP AFF4 UBE3A RAB23 DNMT3A COA3 USP27X IQSEC2 GHRL BPTF LAS1L INS ARL13B PHIP EXOC6B MECP2 SNRPN RERE OTX2 RBMX SIM1 PNPLA6 SKI WAC DPYD POGZ DCC IL17RD POMGNT1 PDE6G HDAC4 SLC25A4 ALMS1 POU3F4 AKT2 PAX6 CCDC141 TRAPPC9 SEMA3A AHI1 MC4R HACE1 TERT BBS2 PKDCC PIK3CA GABRD ARMC5 RP1L1 CRB1 CNGA1 EHMT1 ANOS1 NF2 LARS2 UFD1 HGSNAT SH3KBP1 ARMC5 UCP3 CCDC28B GTF2I MAGEL2 HSD11B1 SHANK3 BBS5 PRPF3 GUCA1B INPP5E PPARG IGFALS FTO GNAS SETD5 ARL6 BBS4 RAI1 XYLT1 TTC8 NR2E3 PCARE IFT172 MAK MEG3 ADCY3 UPF3B SMC1A NDN PROK2 SOX2 DUSP6 POMC HCFC1 COL10A1 MKKS SMC3 FSCN2 ADNP GNAS-AS1 CA4 ALB MC4R NIN SNRPN IFT27 AKT1 RGR AHR PRPF4 MOG HDAC8 HERC2 ZNF711 TUB NDNF LRAT CEP290 DLG3 DYRK1B SCAPER CRX EP300 DLK1 KIAA1549 KCNJ18 MAGEL2 PROKR2 MLXIPL KIDINS220 FXR1 LZTFL1 BBS12 PRPF31 IQSEC2 PRPF6 AGRP HCRT BBS2 MOG APOE GNAS NRL PRKAR1A BAZ1B LAS1L RDH12 ARL6 COMT HDAC8 FLII ARHGEF6 FOXP1 AIP KCNAB2 C8ORF37 PHF6 GNAS RPS6KA3 PRKAR1A CTSH CEL OCA2
Protein Mutations 3
G20210A P12A W64R