SNPMiner Trials (Home Page)
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 ageSecondary 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 ageDescription: 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 ageDescription: 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 ageMeasure: 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 ageDescription: 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 yearsDescription: 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 yearsDescription: 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 monthsDescription: 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 yearsDescription: 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 monthsDescription: Caries and enamel defects (molar incisor hypomineralization, MIH) determined at a dental examination at age 6 years.
Measure: Dental health Time: 6 yearOther 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 ageDescription: 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 ageDescription: Prescribed medicine for infections. Types and length of infections
Measure: Infections Time: 3-10 years of ageDescription: 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 ageDescription: 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 ageDescription: Questionnaires will be administered to the parents.
Measure: Behavioral and psychopathological dimensions. Time: 6- 10 years of ageDescription: MRI scanning of the Brain
Measure: MRI scanning of the Brain Time: 10 years of ageDescription: 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 ageDescription: 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 ageDescription: 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 ageDescription: 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 ageDescription: 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 ageDescription: Measured by plethysmography (sRaw) at age 3, 4, 5, 6, 8 and 10 years.
Measure: Airway resistance Time: 3-10 years of ageDescription: 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 ageDescription: 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 ageDescription: Measurement of fractional exhaled nitric oxide (FeNO) at age 6, 8 and 10 years
Measure: Airway inflammation: Time: 6-10 years of ageDescription: 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 age2 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 gestationSecondary 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 yearsDescription: 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 visitDescription: 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 deliveryDescription: 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 yearDescription: 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 yearsDescription: Genotype at the rs12936231 SNP
Measure: Child 17q21 Genotype Time: 3 years