SNPMiner Trials by Shray Alag


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Report for Mutation N363S

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 5 clinical trials

Clinical Trials


1 The Role of Glucocorticoid Receptor SNPs in Receptor Function and Metabolic Disease

Background: - Glucocorticoids are primary stress response hormones released from the adrenal gland when an individual is under stress. Chronic or ongoing elevation of these hormones due to prolonged stress or medical treatments can have numerous harmful effects. Researchers are interested in learning more about how these hormones affect cell growth, development, and death. To study glucocorticoid hormones, researchers plan to use the medication dexamethasone, which affects the parts of cells that respond to glucocorticoid hormones. Objectives: - To study glucocorticoid stress hormones in healthy individuals before and after receiving dexamethasone. Eligibility: - Healthy individuals at least 18 years of age. - Participants must not be using certain medications that may affect the dexamethasone test, including hormonal contraception, steroid-based drugs, and some antidepressants. Design: - This study will require an initial screening visit and a second study visit. The visits are estimated to require about 1 to 2 hours of participation over a period of up to 14 days. - Participants will be screened at visit 1 with a full physical examination and medical history, and an initial blood sample for testing. - For visit 2, participants will be asked to abstain from all food and drinks except for water for 12 hours before the appointment, and will take one tablet of dexamethasone 9 hours before the appointment. - Participants will have a second blood sample taken during visit 2, and will receive a snack after the blood is drawn.

NCT01143493 Glucose Homeostasis Protein Metabolism Lipid Metabolism Respiratory Function Connective Tissue Metabolism
MeSH: Metabolic Diseases

The two-sided alternative hypothesis is that there is a trend(homozygous wild-type to heterozygous to homozygous for the minor allele) in change from baseline.. Measure gene expression fold changes by microarray analysis after ex vivo glucocorticoid exposure of macrophages and lymphocytes; validation of affected RNA (elevated or decreased expression) through PCR analysis.. The secondary null hypotheses are that there are no differences among genotypes in fold-change for expression level (measured by RT-PCR for the genes selected by the microarray analysis as having differential expression), and the two-sided alternative is that there are trends.. - INCLUSION CRITERIA FOR PART 1 AND 2: - Male or female 18 years of age or older at the time of enrollment - Must be a participant in the EPR study - Are genotyped and determined to be heterozygote or homozygote carriers of one of the two hGR SNPs (hGR9B A3669G and hGR N363S) or are wild type at the SNP location - Able to understand and provide written informed consent to participate in the study - Able to travel to the CRU - Willing and able to fast for periods of up to 12 hours during the study - Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. --- A3669G --- --- N363S ---

- Active coronary artery disease (angina) or moderate to severe heart failure stage New York Heart Association III-IV - Renal failure - Glaucoma - Uncontrolled psychiatric disorders such as bipolar disorder or schizoaffective disorder - Active systemic fungal infection - Prior hypersensitivity reaction to Dexamethasone - Currently receiving treatment for cancer (certain cancers, like lung cancer make adrenocorticotropic hormone (ACTH), and all induce stress) - Any condition that, in the investigator's opinion, places the participant at undue risk for complications - INCLUSION CRITERIA FOR PART 1 AND 2: - Male or female 18 years of age or older at the time of enrollment - Must be a participant in the EPR study - Are genotyped and determined to be heterozygote or homozygote carriers of one of the two hGR SNPs (hGR9B A3669G and hGR N363S) or are wild type at the SNP location - Able to understand and provide written informed consent to participate in the study - Able to travel to the CRU - Willing and able to fast for periods of up to 12 hours during the study - Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. --- A3669G --- --- N363S ---

PRIMARY OBJECTIVE: Investigate in vivo the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in steroid responsiveness by performing a modified dexamethasone suppression test and comparing responses by genotype. --- N363S ---

SECONDARY OBJECTIVE: Investigate the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in human steroid responsiveness by comparing (across genotypes) gene expression profiles of isolated macrophages and lymphocytes exposed ex vivo to corticosteroids. --- N363S ---

Primary Outcomes

Description: The null hypothesis for this endpoint (primary hypothesis for this study) is that there is no difference among genotypes in the change from baseline cortisol level. The two-sided alternative hypothesis is that there is a trend(homozygous wild-type to heterozygous to homozygous for the minor allele) in change from baseline.

Measure: Measure the change in serum cortisol levels after modified dexamethasone suppression test

Time: baseline level in first visit, posttreatment level in second visit

Secondary Outcomes

Description: The secondary null hypotheses are that there are no differences among genotypes in fold-change for expression level (measured by RT-PCR for the genes selected by the microarray analysis as having differential expression), and the two-sided alternative is that there are trends.

Measure: Measure gene expression fold changes by microarray analysis after ex vivo glucocorticoid exposure of macrophages and lymphocytes; validation of affected RNA (elevated or decreased expression) through PCR analysis.

Time: The cells are cultured from blood drawn from participants at the first clinic visit.

2 Observational Cohort Study on Difference in Glucocorticoid-induced Adrenal Insufficiency in Patients With Rheumatoid Arthritis Related to Different Sensitivity Polymorphisms in the Glucocorticoid Receptor Gene

Development of glucocorticoid (GC)-induced adrenal insufficiency is a serious adverse effect of GC treatment. It is today not possible to predict this adverse effect. The project aims at investigating a possible individual aspect, which may render subjects more or less sensitive to glucocorticoids, and thereby influence development of GC induced adrenal insufficiency. The hypothesis is that subjects with one or another of the polymorphisms in the GC receptor gene will either have increased or diminished GC sensitivity. This may be responsible for differences in development of GC induced adrenal insufficiency.

NCT01411046 Rheumatoid Arthritis Diagnostic Test: Synacthen test
MeSH: Arthritis Arthritis, Rheumatoid Adrenal Insufficiency
HPO: Adrenal insufficiency Arthritis Polyarticular arthritis Rheumatoid arthritis

Patients with or without these polymorphisms were invited to a Synacthen® test, but patients with a mixed hetero- and homozygote genotype were not Exclusion Criteria: - Other major organ disease - Females pregnant - Females not willing to pause estrogen-containing medications 6 weeks prior to Synacthen® test - unable to give a written informed content Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Adrenal Insufficiency Blood is sampled from patients with rheumatoid arthritis (RA), fulfilling the inclusion criteria and patients are genotyped for the SNPs N363S, BclI, ER22/23EK and 9β and grouped according to haplotypes. --- N363S ---

Primary Outcomes

Description: test for adrenal function by stimulation test (Synacthen test)

Measure: adrenal insufficiency

Time: upon first visit within average 1 month

Secondary Outcomes

Description: test by questionnaires

Measure: quality of life

Time: upon inclusion (baseline)

Description: DXA and bone markers

Measure: Bone Density status

Time: results from latest DXA scan performed in routine settings, bonemarkers upon inclusion (baseline)

Description: BMI, waist-, hip- circumferencia

Measure: body composition

Time: upon inclusion (baselline)

Description: blood lipids, abdominal obesity, blood pressure, fasting plasma glucose

Measure: metabolic syndrome

Time: upon inclusion (baseline)

3 Prevalence of Adrenal Insufficiency in Kidney Transplanted Patients (NTx) in Glucocorticoid Treatment

The primary purpose of this study is to determine the prevalence of adrenal insufficiency in a population of patients with kidney transplants receiving low dose prednisone treatment. Development of glucocorticoid-induced adrenal insufficiency is a serious adverse effect to glucocorticoid treatment. The study includes a control group of patients with kidney failure currently treated in dialysis, who are not in glucocorticoid treatment. Individual genotyping is performed to determine the haplotype of glucocorticoid receptor polymorphisms: N363 S, BclI, ER23/23EK and 9β in all the patients with the purpose of investigating this as a risk factor for the development of adrenal insufficiency. The hypothesis is that subjects with one or another of the polymorphisms in the glucocorticoid receptor gene will either have increased or diminished glucocorticoid sensitivity. Using validated questionnaires assessing the quality of life and functional level of the patients enrolled in the study we aim to establish a link between functional level and biochemically proven adrenal insufficiency. Other secondary outcomes in the study includes bloodpressure, body composition, bone density, metabolic syndrome, inflammation and salivary cortisol profiles.

NCT03136562 Adrenal Insufficiency Diagnostic Test: Synacthen test
MeSH: Adrenal Insufficiency
HPO: Adrenal insufficiency

The primary outcome measure of this study is the result of the Synacthen® test using primarily the level of P-cortisol 30 minutes after the injection of synacthen.. Cutoff for normal adrenal function: 30 min p-cortisol >/= 420 nmol/L.. Registration of history of treatment.. History of treatment with prednisone and other types of glucocorticoids to examine dosage and time of treatment as risk factors.. Quality of life and functional level.. Assessed in all patients enrolled in the study using validated questionnaires as a means to establish a link between functional level and biochemically proven adrenal insufficiency.. Determination of the specific type of glucocorticoid receptor using genotyping in all the patients with the purpose of investigating this as a risk factor for the development of adrenal insufficiency.. Patients are genotyped for 4 polymorphisms (9 beta, ER22/23EK, Bcl1 and N363S) of the glucocorticoid receptor.. Body composition. --- N363S ---

Primary Outcomes

Description: Cutoff for normal adrenal function: 30 min p-cortisol >/= 420 nmol/L.

Measure: The primary outcome measure of this study is the result of the Synacthen® test using primarily the level of P-cortisol 30 minutes after the injection of synacthen.

Time: The time frame of each Synacthen® test is approximately 90 minutes.

Secondary Outcomes

Description: History of treatment with prednisone and other types of glucocorticoids to examine dosage and time of treatment as risk factors.

Measure: Registration of history of treatment.

Time: The registration will take place at the study visit (approximately 90 minutes).

Description: Assessed in all patients enrolled in the study using validated questionnaires as a means to establish a link between functional level and biochemically proven adrenal insufficiency.

Measure: Quality of life and functional level.

Time: Patients receive and fill out the questionnaires prior to their arrival at the study visit and hand them in after the Synacthen® test. Patients receive questionnaires either by mail or at one of their visits in the out patient clinic.

Description: Patients are genotyped for 4 polymorphisms (9 beta, ER22/23EK, Bcl1 and N363S) of the glucocorticoid receptor.

Measure: Determination of the specific type of glucocorticoid receptor using genotyping in all the patients with the purpose of investigating this as a risk factor for the development of adrenal insufficiency.

Time: Blood for genotyping is sampled from each patient at the study visit during the Synacthen® test. The blood samples are stored frozen and analyzed concurrently.

Description: Height, weight, waist and hip circumference.

Measure: Body composition

Time: After the Synacthen® test the height, weight, waist and hip circumference are measured at the study visit.

Description: Results from Dxa-scan.

Measure: Bone density.

Time: The results from latest Dxa-scan performed in rutine settings are collected from the patients on the same day as the Synacthen® test.

Description: Waistline, triglyceride level, HDL cholesterol level, blood pressure and fasting blood sugar is assessed in all the patients.

Measure: Metabolic syndrome.

Time: The waistline and blood pressure are measured at the study visit after the Synacthen® test. The blood samples are collected as part of the test and analyazed on the same day.

Description: Cortisol concentration in saliva.

Measure: Salivary cortisol profiles.

Time: Saliva is sampled from each patient at the study visit as part of the Synacthen® test. The samples are stored frozen and analyzed concurrently after all 60 Synacthen® tests have been performed.

4 The Prevalence of Secondary Adrenal Insufficiency in Patients With Exacerbation of COPD in Glucocorticoid Treatment Related to Differenct Gene Polymorphisms of the Glucocorticoid Receptor Gene

To investigate the correlation between four well-known polymorphisms of the glucocorticoid receptor gene (two with reduced sensitivity versus two with increased sensitivity) and the prevalence of secondary adrenal insufficiency in glucocorticoid-treated patients with exacerbation of COPD.

NCT03140761 Adrenal Insufficiency
MeSH: Adrenal Insufficiency
HPO: Adrenal insufficiency

Inclusion Criteria: - Adult patients > 18 years - Caucasian classified with COPD - Patients with AECOPD being treated with at least 5 days of glucocorticoid (minimum of 180 mg) Exclusion Criteria: - Treated with estrogen-containing medications, including anticonceptiva 6 weeks prior to Synacthen® - Pregnancy or lactation - on regular systemic glucocorticoid therapy before admission to the hospital - People who are detained under the act on the use of coercion in psychiatry - Severe language problems or inability to provide written informed consent Inclusion Criteria: - Adult patients > 18 years - Caucasian classified with COPD - Patients with AECOPD being treated with at least 5 days of glucocorticoid (minimum of 180 mg) Exclusion Criteria: - Treated with estrogen-containing medications, including anticonceptiva 6 weeks prior to Synacthen® - Pregnancy or lactation - on regular systemic glucocorticoid therapy before admission to the hospital - People who are detained under the act on the use of coercion in psychiatry - Severe language problems or inability to provide written informed consent Adrenal Insufficiency Adrenal Insufficiency COPD patients who have received systemic glucocorticoid exceeding the equivalent of 180 mg prednisolone which are homo / heterozygous for the BclI and / or N363S polymorphisms (associated with increased glucocorticoid sensitivity) will have a lower cortisol response in a synacthen® test (greater suppression of adrenal corticosteroid) than the corresponding patients there are wild-type or homo- or heterozygous for the polymorphic ER22 / 23EK and / or 9β (associated with decreased sensitivity). --- N363S ---

Primary Outcomes

Description: test for adrenal function by stimulation test

Measure: Secondary Adrenal insufficiency

Time: average 1 month

Secondary Outcomes

Description: blood lipids, blood pressure, plasma glucose, abdominal obesity, body composition

Measure: Metabolic syndrome

Time: average 1 month

Description: bonemarkers

Measure: Bone mineral loss

Time: average 1 month

Measure: Onset of Diabetes Mellitus

Time: average 1 month

Description: test by questionnaires

Measure: Quality of life

Time: average 1 month

5 Predisposing Factors for the Incidence of Adrenal Crisis in Chronic Adrenal Insufficiency

Within this clinical study patients with chronic adrenal insufficiency will be investigated by clinical and biochemical examination as well as questionnaire to identify predisposing factors for adrenal crisis.

NCT03410160 Adrenal Insufficiency Diagnostic Test: Clinical and biochemical examination.
MeSH: Adrenal Insufficiency
HPO: Adrenal insufficiency

Evaluation of glucocorticoid-receptor-polymorphisms (ER 22/23 EK, N363S, bcl1, 9beta, Tth3l). --- N363S ---

Primary Outcomes

Description: Measurement of hsCRP (mg/dl) and Interleukin-6 (pg/ml) levels. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis exhibit higher hsCRP and Interleukin-6 levels.

Measure: Chronic inflammation (hsCRP, Interleukin-6)

Time: 1 day

Description: Measurement of cortisol-levels (mg/dl) before as well as 60 min and 120 min after ingestion of hydrocortisone. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis exhibit a faster hydrocortisone metabolism.

Measure: Cortisol metabolism

Time: 1 day

Description: Evaluation of hormone replacement therapy with glucocorticoids by a clinical score. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis suffer from under-replacement.

Measure: Replacement therapy with glucocorticoids

Time: 1 day

Description: Evaluation of hormone replacement therapy with mineralocorticoids by a clinical and biochemical assessment. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis suffer from under-replacement.

Measure: Replacement therapy with mineralocorticoids

Time: 1 day

Description: Evaluation of glucocorticoid-receptor-polymorphisms (ER 22/23 EK, N363S, bcl1, 9beta, Tth3l). Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a higher prevalence of glucocorticoid-receptor-polymorphisms.

Measure: Glucocorticoid-receptor-polymorphisms

Time: 1 day

Description: Evaluation of catecholamine-levels (ng/l). Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a more pronounced catecholamin-deficit.

Measure: Catecholamine-levels

Time: 1 day

Description: Evaluation of patient education by questionnaire. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a worse education status.

Measure: Patient education

Time: 1 day


HPO Nodes


Adrenal insufficiency
Genes 136
SNRPN CYP11A1 SNORD116-1 VAMP7 NFKB2 PCSK1 TXNRD2 PEX1 SGPL1 IARS2 PEX14 BCOR HSD11B2 SOX9 SMARCB1 PEX2 TRNH HSD3B2 AIRE PEX10 CYP11B2 IPW GATA4 LHX4 NF2 PEX1 ND4 NPAP1 NNT PEX13 MCM4 TRNL1 CYP17A1 MKRN3 TXNRD2 LIPA ABCD1 PEX5 AAAS PEX12 PEX13 TCTN3 SRY TRNQ PCSK1 NR5A1 PEX19 TRNS2 AAAS RBM28 MAP3K1 PEX10 POMC HSD11B2 PEX6 CDH23 TRNS1 NR3C2 PEX3 PEX5 POR RBM28 PEX11B BRAF PWRN1 GK GLI3 MRAP SCNN1B AIRE CYP11A1 PEX14 ABCC8 PEX3 ZFPM2 NR0B1 NDN COX1 MAGEL2 SAA1 CDH23 MKRN3-AS1 STAR MRAP CTNNB1 TRNF PEX16 PEX19 PEX16 ND1 NR3C1 PWAR1 PEX12 TRNW COX3 CYP11B2 SAMD9 MEN1 CYP11B1 MC2R CYP11A1 PEX26 PEX2 WT1 NR0B1 PEX5 PEX6 GMPPA COX2 PDGFB DMRT3 PEX6 AIP TBX19 SNORD115-1 GLI3 MC2R POMC HBB SUFU KCNJ11 CYP11B2 ND6 PEX26 PEX11B TRAPPC11 MRPS7 STEAP3 ND5 PROP1 TBX19 HSD17B4 CYP11B1 HERC2 NFKB2 WWOX
Rheumatoid arthritis
Genes 28
NFKBIL1 ACP5 PTPN2 LACC1 IL2RB SLC22A4 IL6 HLA-DRB1 PTPN22 CD244 PTPN22 ANKRD55 STAT4 ANKRD55 IL2RB PADI4 PTPN22 IL2RA CIITA STAT4 IL2RA IL10 CD247 PTPN2 CD247 GCH1 MIF DCLRE1C
Arthritis
Genes 263
COL5A2 HPGD COL1A1 CANT1 HJV TRPV4 CCR1 HNF1B PTPN2 LACC1 BTK TFR2 HOXD10 CLCN7 COL9A2 PTPN22 MMP2 NLRP3 STAT4 GHR RNF168 TREX1 COL9A3 PADI4 SLC40A1 WIPF1 COL2A1 MMP14 RASGRP1 PRKCD SEC61A1 SLC37A4 COL2A1 HNF1B TBX1 PTPN22 STAT4 MEFV AEBP1 COL2A1 IL2RB HLA-DRB1 HGD PSTPIP1 ANKRD55 FBN1 GBA HPGD CCN6 ANKRD55 FGFR3 NOD2 ACAN COMP HPRT1 AGA IRF5 NLRC4 MUC1 IL12B GNAS HPGD MATN3 CASP10 ASAH1 COMP MYH14 HIRA SLCO2A1 SLC22A4 HLA-B FRZB CD244 PRG4 COL11A2 LMX1B TNFRSF1A ACAN TGFB3 STAT4 COL11A1 IL10 MEFV LRP6 RAG2 IFIH1 TRAPPC2 LBR IL10 COL5A1 IGHM LEMD3 HLA-DRB1 DNASE1 COMP SH3KBP1 NFKBIL1 IL12A-AS1 IL12A ARVCF COL2A1 CLCN7 IL23R KIF7 DNASE1L3 SEC24C IL6 FCGR2A COL9A3 SLC37A4 AIP SPTB HPRT1 GDF5 COL2A1 JMJD1C TCF3 IL2RB COMP HLA-B TRAPPC2 COL5A1 HNF4A F9 COMT UFD1 SMAD3 STAT3 HPRT1 HGD SPTA1 GJB6 ATP7B COL9A1 F8 BLNK PTPN22 APOE UMOD TREX1 MMP13 ZNF687 NLRP3 GJB2 PSMB9 PTPN22 TF CD79B COL2A1 MMP13 LMNA UFSP2 ERAP1 LRBA COPA CCR6 COL9A2 ABCG8 TRPS1 CD247 MIF C1R GP1BB PFKM LRRC8A FAS PHEX UMOD ANKH G6PC FCGR2B COL2A1 CCN6 IGLL1 CAV1 PSTPIP1 NLRP12 KIF22 ANKH SPP1 ATP7B CTLA4 CD79A SLC4A1 RNASEH2B EPCAM FAS NLRP3 CCN2 WAS COL1A1 PSMB4 UFSP2 TLR4 STAT4 MVK ACP5 MATN3 HPRT1 SLC12A3 BTK MTHFD1 ADA2 RAG1 PIK3R1 SCARB2 OCRL ADAR HLA-DRB1 RREB1 COL11A2 RNASEH2C PTPN22 GPR101 IL36RN CIITA C1QA SLC26A2 NLRP3 PHEX RNASEH2A KLRC4 COL2A1 ZMPSTE24 CD247 CFI UBAC2 BTK HLA-B DNAJB11 GCH1 FAS C4A COL11A2 EPB42 PRPS1 IRAK1 EXT2 MEFV MEFV GLA ACAN FASLG MVK MATN3 CLCNKB IL2RA EXT1 ASPN COL3A1 IL2RA TBX1 COL9A1 NOD2 HLA-C COL2A1 ANK1 TRPV4 SAMHD1 PTPN2 SMAD3 MLX DCLRE1C