SNPMiner Trials by Shray Alag


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Report for SNP rs12936231

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 2 clinical trials

Clinical Trials


1 Vitamin D Supplementation During Pregnancy for Prevention of Asthma in Childhood: An Interventional Trial in the ABC (Asthma Begins in Childhood) Cohort

The aim of this study is to prevent asthma symptoms (recurrent wheeze) in childhood by supplementation with high dose vitamin D to the mother during pregnancy. Participants are mothers and children of the ABC (Asthma Begins in Childhood) cohort. Mothers are recruited during pregnancy and receive daily supplement with 2400 IU of Vitamin D3 or placebo from week 24 og gestation to 1 week after delivery. In addition all mothers are advised to take the recommended dose of 400 IU vitamin D daily. The mothers in ABC also participate in an interventional trial with fish oil supplementation, and the vitamin D randomization is stratified by fish oil treatment group. The child is followed with acute and planned vits at the research unit, and wheeze is diagnosed according to predefined algorithms.

NCT00856947 Asthma Dietary Supplement: Cholecalciferol D3 Other: Placebo tablet
MeSH: Asthma
HPO: Asthma

We will compute hazard ratios for the reduction in asthma/wheeze risk associated with prenatal supplementation, stratified by rs12936231.

rs12936231 is a functional SNP influencing expression of ORMDL3, and given the role of ORMDL3 as a key sphingolipid biosynthesis regulator, we will subsequently investigate the relative abundance of sphingolipids between those in the vitamin D Intervention arm and those in the placebo group, stratified by 17q21 genotype.

Finally we will identify interactions between prenatal vitamin D supplementation, rs12936231 genotype and sphingolipid metabolism in the risk of asthma/wheeze by age three.. Dental health.

Primary Outcomes

Description: Age at onset of persistent wheeze diagnosed according to predefined algorithm of recurrent troublesome lung symptoms, response to treatment and relapse after withdrawal of treatment

Measure: Persistent wheeze

Time: 0 to 3 years of age

Secondary Outcomes

Description: Main analysis: • Number of lower respiratory tract infections registered in daily diaries Secondary analyses: Acute otitis media Number of upper respiratory tract infections Number of other infections Total number of infections

Measure: Infections

Time: 0 to 3 years of age

Description: Allergic sensitization at 6 and/or 18 months assessed by skin prick test and specific IgE in blood

Measure: Allergic sensitization

Time: 6 and 18 months of age

Description: Age at onset of eczema diagnosed prospectively by research doctors according to predefined algorithm based upon Hanifin and Rajka criteria

Measure: Eczema

Time: 0 to 3 years of age

Measure: Mothers levels of 25-OH-Vitamin D, PTH, Calcium, alkaline phosphatase

Time: 1 week after delivery

Measure: Growth

Time: 0 to 3 years of age

Description: Age at onset of severe asthma exacerbation diagnosed by predefined criteria of acute severe asthma requiring oral/high dose inhaled steroids or acute hospital contact

Measure: Asthma exacerbations

Time: 0 to 3 years of age

Description: Main analysis: • Cognitive development assessed at 2½ years using the cognitive part of Bayley Scales of Infant and Toddler Development, third edition Secondary analyses: Milestone development monitored prospectively by the parents using a registration form based on The Denver Development Index and WHO milestones registration (combined assessment by principal component analysis) Language development assessed at 1 and 2 years of age with the Danish version of The MacArthur Bates Communicative Developmental Inventory (CDI) The child´s general development (language, fine and gross motor, social and problem solving) at 3 years of age assessed with Ages and stages Questioner, third edition (ASQ-3)

Measure: Neurological development

Time: 0-3 years

Description: Main analysis: • Body composition (fat mass and bone mineral density) assessed by DEXA scan at 3 years of age Secondary analysis • Development of BMI from birth to 3 years assesses longitudinally in the research clinic

Measure: Growth

Time: 0-3 years

Description: Main analysis Immune status at 18 months measured in stimulated whole blood as cytokine release (combined assessments by prinicipal component analyses) Secondary analyses Composition of immune cell subsets in whole blood at birth and at 18 months of age

Measure: Systemic immune status

Time: 18 months

Description: Immune status measured in airway mucosal lining fluid at 4 weeks and 2 years of age (combined assessments by prinicipal component analyses for each age point)

Measure: Airway mucosal immune status

Time: 4 weeks and 2 years

Description: In a secondary analyses, we will determine the effect of 17q21 genotype on the efficacy of vitamin D supplementation in the prevention of asthma/wheeze. We will compute hazard ratios for the reduction in asthma/wheeze risk associated with prenatal supplementation, stratified by rs12936231. rs12936231 is a functional SNP influencing expression of ORMDL3, and given the role of ORMDL3 as a key sphingolipid biosynthesis regulator, we will subsequently investigate the relative abundance of sphingolipids between those in the vitamin D Intervention arm and those in the placebo group, stratified by 17q21 genotype. Finally we will identify interactions between prenatal vitamin D supplementation, rs12936231 genotype and sphingolipid metabolism in the risk of asthma/wheeze by age three.

Measure: 17q21 genotype and sphingolipid metabolites

Time: 6 months

Description: Caries and enamel defects (molar incisor hypomineralization, MIH) determined at a dental examination at age 6 years.

Measure: Dental health

Time: 6 year

Other Outcomes

Description: Asthma diagnosed from age 3 to 10 years based on the same predefined algorithm of recurrent troublesome lung symptoms, response to treatment after withdrawal of treatment, which was used for persistent wheeze at age 0-3 in phase 1 of the study. Primary outcome in phase 2 is current asthma at specific visits till age 10 years, which is diagnosed in children fulfilling the persistent wheeze algorithm at any point during the first 10 years of life and still needing inhaled corticosteroids at specific visits (3, 4, 5, 6, 8 and 10 years of age) to control the symptoms.

Measure: Asthma

Time: 3-10 years of age

Description: Spirometry measuring airflow assessed by FEV1, MMEF and FEV1/FVC ratio at age 5, 6, 8 and 10 years.

Measure: Lung function measurements

Time: 5-10 years of age

Description: Prescribed medicine for infections. Types and length of infections

Measure: Infections

Time: 3-10 years of age

Description: Anthropometrics: Clinical follow up on the development of weight in kg (calibrated digital weight scales), height in cm (Harpenden stadiometer), waist-, thorax- and head circumference in cm (using tape; 3 times each) at every visit till age 10 years assessed longitudinally in the research clinic.

Measure: Growth

Time: 3- 10 years of age

Description: A 2,5 hours cognitive evaluation at 10 years of age. Cognitive functions from a broad spectrum of cognitive domains will be assessed with subtests both using paper pencil tests and Cambridge Neuropsychological Test Automated Battery .

Measure: Cognitive function

Time: 10 years of age

Description: Questionnaires will be administered to the parents.

Measure: Behavioral and psychopathological dimensions.

Time: 6- 10 years of age

Description: MRI scanning of the Brain

Measure: MRI scanning of the Brain

Time: 10 years of age

Description: Age at onset of eczema diagnosed prospectively by research doctors according to predefined algorithm based upon Hanifin and Rajka criteria

Measure: Eczema

Time: 3-10 years of age

Description: Allergic sensitization at 6 and 10 years of age assessed by skin prick test (ALK-Abelló, Denmark) and specific IgE in blood (ImmunoCAP, PHarmacia Diagnostics AB, Sweden).

Measure: Allergic sensitization/atopy

Time: 6-10 years of age

Description: Immune status measured in airway mucosal lining fluid at 3, 6 and 10 years of age (combined assessments by principal component analyses for each age point).

Measure: Airway mucosal immune status

Time: 3-10 years of age

Description: Allergic rhinitis will be diagnosed by combining allergic sensitization with symptom recording of troublesome congestion or sneezing or runny nose upon relevant exposure to allergens at age 3, 4, 5, 6, 8 and 10 years.

Measure: The diagnose allergic rhinitis

Time: 3-10 years of age

Description: Age at onset and number of severe asthma exacerbation diagnosed by predefined criteria of acute severe asthma requiring oral/ high dose inhaled steroids or acute hospital contact

Measure: Asthma exacerbations:

Time: 3-10 years of age

Description: Measured by plethysmography (sRaw) at age 3, 4, 5, 6, 8 and 10 years.

Measure: Airway resistance

Time: 3-10 years of age

Description: Multiple breath wash-out using SF6 and N2 as inert gasses to determined LCI, Scond and Sacin at ages 3, 4 and 5 years.

Measure: Airway resistance

Time: 3-5 years of age

Description: Provocative dose of methacholine leading to a 20% drop in FEV1 from baseline (PD20 value) at age 6 years.

Measure: Bronchial reactivity:

Time: at 6 years of age

Description: Measurement of fractional exhaled nitric oxide (FeNO) at age 6, 8 and 10 years

Measure: Airway inflammation:

Time: 6-10 years of age

Description: Body composition measured as fat mass, lean mass, bone mineral content (BMC) and bone mineral density assessed (BMD) through DXA scans at 3 and 6 years of age. Body impedance measurements at 10 years of age.

Measure: Body composition

Time: 3-10 years of age

2 Randomized Trial: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART)

Vitamin D supplementation given to pregnant women will prevent asthma in their offspring and children.

NCT00920621 Asthma Dietary Supplement: Vitamin D 3 cholecalciferol Dietary Supplement: Vitamin D3
MeSH: Asthma
HPO: Asthma

Genotype at the rs12936231 SNP.

We will compute hazard ratios for the reduction in asthma/wheeze risk associated with prenatal supplementation, stratified by rs12936231.

rs12936231 is a functional SNP influencing expression of ORMDL3, and given the role of ORMDL3 as a key sphingolipid biosynthesis regulator, we will subsequently investigate the relative abundance of sphingolipids between those in the vitamin D Intervention arm and those in the placebo group, stratified by 17q21 genotype.

Finally we will identify interactions between prenatal vitamin D supplementation, rs12936231 genotype and sphingolipid metabolism in the risk of asthma/wheeze by age three.

Primary Outcomes

Description: Parental report of physician diagnosis of asthma or occurrence of recurrent wheeze in the child's first 3 years of life ascertained from questionnaires administered every 3 months. *For some variables the "negative" count incorporates "negative and indeterminate."

Measure: Asthma or Recurrent Wheeze in First 3 Years of Life

Time: First 3 years of life.

Description: Maternal serum 25-hydroxyvitamin D measurement at third trimester during pregnancy

Measure: Achieved Maternal 25(OH)D Level of ≥ 30 ng/mL at Third Trimester Sampling.

Time: 32-38 weeks gestation

Secondary Outcomes

Description: Child positive-specific IgE tests from blood collection at 3 year visit.

Measure: Child Positive-specific IgE Tests From Blood Collection at 3 Year Visit.

Time: 3 years

Description: Child serum 25-hydroxyvitamin D measurement from blood collection at 1 year visit.

Measure: Child Serum 25-hydroxyvitamin D Measurement From Blood Collection at 1 Year Visit.

Time: 1 year visit

Description: Parental report of physician diagnosis of eczema with rash in typical distribution in the child's first 3 years of life ascertained from questionnaires administered every 3 months. *For some variables the "negative" count incorporates "negative and indeterminate."

Measure: Parental Report of Physician Diagnosed Eczema (With Rash) in the Child's First 3 Years of Life.

Time: Child's first 3 years of life.

Description: Parental report of physician diagnosis of lower respiratory tract infection (LRI) in the child's first 3 years of life. LRI defined as physician diagnosed bronchitis, bronchiolitis, croup, or pneumonia ascertained from questionnaires administered every 3 months.

Measure: Parental Report of Physician Diagnosis of Lower Respiratory Tract Infection in the Child's First 3 Years of Life.

Time: Child's first 3 years of life.

Description: Child serum 25-hydroxyvitamin D measurement from blood collection at 3 year visit.

Measure: Child Serum 25-hydroxyvitamin D Measurement From Blood Collection at 3 Year Visit.

Time: Blood collection at childs' 3 year visit.

Description: Any allergic sensitization in the child's first 3 years of life. *For some variables the "negative" count incorporates "negative and indeterminate."

Measure: Any Allergic Sensitization in the Child's First 3 Years of Life.

Time: Child's first 3 years of life.

Description: Mass Spec Vitamin D value from cord blood at delivery

Measure: Mass Spec Vitamin D Value From Cord Blood at Delivery

Time: Blood collection at delivery

Description: Mass spec measured relative abundance of five metabolites of the sphingolipid metabolism pathway in plasma samples extracted at the year one visit.

Measure: Sphingolipid Profile

Time: 1 year

Description: Mass spec measured relative abundance of five metabolites of the sphingolipid metabolism pathway in plasma samples extracted at the year three visit.

Measure: Sphingolipid Profile

Time: 3 years

Description: Genotype at the rs12936231 SNP

Measure: Child 17q21 Genotype

Time: 3 years


HPO Nodes


Asthma
Genes 138
DNAH9 COL5A2 DNAH11 NFKB2 TDGF1 DDX41 SPAG1 ARMC4 GP1BA GAS2L2 CCDC151 ERCC2 TNF SPINK5 GP1BB GAS1 TGIF1 CCL11 CDON DLL1 CFAP221 PTGER2 TBX21 LRBA RSPH4A CFTR FLG NME8 DNAAF4 ZIC2 SCGB3A2 CCDC65 SDHD ADRB2 TBX1 GP1BB SIX3 IDS NODAL NSUN2 ELOVL4 PEPD CARMIL2 CFAP300 FGF8 GP9 FOXJ1 DNAI1 CASP8 DOCK8 CCDC151 DISP1 IL13 CCNO ALMS1 RSPH1 CCDC39 STK36 MUC7 NOD2 CARD11 CCDC28B DNAL1 DNAH1 ZMYND10 RSPH3 RSPH9 MS4A2 PLA2G7 HNMT DRC1 NKX2-1 SHH COL1A1 CCDC103 SPINK5 FGFR1 DNAAF3 MTOR HIRA LRRC56 LRRC6 GAS8 CFAP298 NEK9 CCDC40 IL4R PGM3 DOCK8 DNAAF2 GLI2 RREB1 TGFB1 PTCH1 GRHL2 SIK3 SCN4A BBS1 TALDO1 DNAAF1 NKX2-1 OFD1 TRAIP PLCG2 HLA-G COL5A1 ALMS1 DNAI2 BCL11B LIG4 GTF2H5 PGM3 ARVCF PEX5 CDSN SEC24C DNAAF6 DNAH5 CCDC114 ADA PLA2G7 JMJD1C DNAJB13 RPGR FOXH1 ALOX5 TTC25 FCGR2A TBX1 COMT COX4I2 UFD1 SPEF2 SUFU DNAAF5 LIFR MCIDAS HYDIN