ArticleAnnals of neurology2011
Rare variants in the CYP27B1 gene are associated with multiple sclerosis.
Article in Annals of neurology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.
- The Association Between Genetic Polymorphism rs703842 in CYP27B1 and Multiple Sclerosis: A Meta-Analysis.Medicine · 2016Pooled it
- Genetic Risk in Multiple Sclerosis: Susceptibility, Modifiers and Unresolved Questions.Neurology and therapy · 2026Review
- Multiple sclerosis pathophysiology: a comprehensive review of genetic, environmental, and immunological drivers.Inflammopharmacology · 2025Review
- RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system.Journal of advanced research · 2025Review
- Article
- Identification and Association ofCurrent issues in molecular biology · 2025Article
- Multiple sclerosis: molecular pathogenesis and therapeutic intervention.Signal transduction and targeted therapy · 2025Review
- Impact of the CYP27B1 p.R389H mutation on protein stability and function: implications for multiple sclerosis pathogenesis.Scientific reports · 2025Article
- Increased burden of rare variants in GWAS associated genes in familial multiple sclerosis.Scientific reports · 2025Article
- Exome sequencing reveals low-frequency and rare variant contributions to multiple sclerosis susceptibility in Turkish families.Scientific reports · 2025Article
- Genetic Polymorphisms in Cytochrome P450 Enzymes Involved in Vitamin D Metabolism and the Vitamin D Receptor: Their Clinical Relevance.Journal of personalized medicine · 2025Review
- The link between gut microbiota and multiple sclerosis from the perspective of barrier function.Frontiers in immunology · 2025Review
- The impact of genetic variants related to vitamin D and autoimmunity: A systematic review.Heliyon · 2024Article
- Epstein-Barr virus, vitamin D and the immune response: connections with consequences for multiple sclerosis.Frontiers in immunology · 2024Review
- Vitamin D Receptor Gene Polymorphism Predicts the Outcome of Multidisciplinary Rehabilitation in Multiple Sclerosis Patients.International journal of molecular sciences · 2023Article
- Genomic mechanisms controlling renal vitamin D metabolism.The Journal of steroid biochemistry and molecular biology · 2023Article
- Internal m7G methylation: A novel epitranscriptomic contributor in brain development and diseases.Molecular therapy. Nucleic acids · 2023Review
- Immunomodulatory actions of vitamin D in various immune-related disorders: a comprehensive review.Frontiers in immunology · 2023Review
- A Whole-Genome Sequencing Study Implicates GRAMD1B in Multiple Sclerosis Susceptibility.Genes · 2022Article
- Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action.Inflammopharmacology · 2022Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveMultiple sclerosis (MS) is a complex neurological disease. Genetic linkage analysis and genotyping of candidate genes in families with 4 or more affected individuals more heavily loaded for susceptibility genes has not fully explained familial disease clustering.
methodsWe performed whole exome sequencing to further understand the heightened prevalence of MS in these families.
resultsForty-three individuals with MS (1 from each family) were sequenced to find rare variants in candidate MS susceptibility genes. On average, >58,000 variants were identified in each individual. A rare variant in the CYP27B1 gene causing complete loss of gene function was identified in 1 individual. Homozygosity for this mutation results in vitamin D-dependent rickets I (VDDR1), whereas heterozygosity results in lower calcitriol levels. This variant showed significant heterozygous association in 3,046 parent-affected child trios (p = 1 × 10(-5)). Further genotyping in >12,500 individuals showed that other rare loss of function CYP27B1 variants also conferred significant risk of MS, Peto odds ratio = 4.7 (95% confidence interval, 2.3-9.4; p = 5 × 10(-7)). Four known VDDR1 mutations were identified, all overtransmitted. Heterozygous parents transmitted these alleles to MS offspring 35 of 35× (p = 3 × 10(-9)).
interpretationA causative role for CYP27B1 in MS is supported; the mutations identified are known to alter function having been shown in vivo to result in rickets when 2 copies are present. CYP27B1 encodes the vitamin D-activating 1-alpha hydroxylase enzyme, and thus a role for vitamin D in MS pathogenesis is strongly implicated.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.