ArticleAnnals of neurology2015
Genetic modifiers of ambulation in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study.
Article in Annals of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03439670 (A Phase IIb Randomized, Double-blind, Parallel Group, Placebo- and Active-controlled Study With Double-Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys With Duchenne Muscular Dystrophy), which is not on this map. Cited by 82 papers, 5 of them syntheses that pooled it.
What it found
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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.
A Phase IIb Randomized, Double-blind, Parallel Group, Placebo- and Active-controlled Study With Double-Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys With Duchenne Muscular Dystrophy (DMD)
Who cites it
82 citing papers in PubMed, 5 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Predictors of Loss of Ambulation in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis.Journal of neuromuscular diseases · 2024Pooled it
- Pooled it
- The clinical course of Duchenne muscular dystrophy in the corticosteroid treatment era: a systematic literature review.Orphanet journal of rare diseases · 2021Pooled it
- The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review.Orphanet journal of rare diseases · 2017Pooled it
- Corticosteroids for the treatment of Duchenne muscular dystrophy.The Cochrane database of systematic reviews · 2016Pooled it
- Trial
- Exon-skipping therapies for DMD in Kazakhstan: Progress and challenges.Journal of neuromuscular diseases · 2026Article
- Creatine/Creatinine Ratio and Myostatin as Biomarkers to Monitor Muscle Function in Duchenne Muscular Dystrophy Patients.Journal of cachexia, sarcopenia and muscle · 2026Observational
- Molecular genetics of dystrophinopathy.Journal of human genetics · 2025Review
- The Potential of Disease Progression Modeling to Advance Clinical Development and Decision Making.Clinical pharmacology and therapeutics · 2025Review
- Review
- The complex landscape of DMD mutations: moving towards personalized medicine.Frontiers in genetics · 2024Review
- The IAAM LTBP4 Haplotype is Protective Against Dystrophin-Deficient Cardiomyopathy.Journal of neuromuscular diseases · 2024Article
- Standardization of zebrafish drug testing parameters for muscle diseases.Disease models & mechanisms · 2024Article
- Natural history of Becker muscular dystrophy: a multicenter study of 225 patients.Annals of clinical and translational neurology · 2023Article
- Association between neurodevelopmental impairments and motor function in Duchenne muscular dystrophy.Annals of clinical and translational neurology · 2023Article
- Is it time for genetic modifiers to predict prognosis in Duchenne muscular dystrophy?Nature reviews. Neurology · 2023Review
- Upper Limb Changes in DMD Patients Amenable to Skipping Exons 44, 45, 51 and 53: A 24-Month Study.Children (Basel, Switzerland) · 2023Article
- Diverse effector and regulatory functions of fibro/adipogenic progenitors during skeletal muscle fibrosis in muscular dystrophy.iScience · 2023Article
- Biomarkers in Duchenne Muscular Dystrophy: Current Status and Future Directions.Journal of neuromuscular diseases · 2023Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveWe studied the effects of LTBP4 and SPP1 polymorphisms on age at loss of ambulation (LoA) in a multiethnic Duchenne muscular dystrophy (DMD) cohort.
methodsWe genotyped SPP1 rs28357094 and LTBP4 haplotype in 283 of 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS). Median ages at LoA were compared by Kaplan-Meier analysis and log-rank test. We controlled polymorphism analyses for concurrent effects of glucocorticoid corticosteroid (GC) treatment (time-varying Cox regression) and for population stratification (multidimensional scaling of genome-wide markers).
resultsHispanic and South Asian participants (n = 18, 41) lost ambulation 2.7 and 2 years earlier than Caucasian subjects (p = 0.003, <0.001). The TG/GG genotype at SPP1 rs28357094 was associated to 1.2-year-earlier median LoA (p = 0.048). This difference was greater (1.9 years, p = 0.038) in GC-treated participants, whereas no difference was observed in untreated subjects. Cox regression confirmed a significant effect of SPP1 genotype in GC-treated participants (hazard ratio = 1.61, p = 0.016). LTBP4 genotype showed a direction of association with age at LoA as previously reported, but it was not statistically significant. After controlling for population stratification, we confirmed a strong effect of LTBP4 genotype in Caucasians (2.4 years, p = 0.024). Median age at LoA with the protective LTBP4 genotype in this cohort was 15.0 years, 16.0 for those who were treated with GC.
interpretationSPP1 rs28357094 acts as a pharmacodynamic biomarker of GC response, and LTBP4 haplotype modifies age at LoA in the CINRG-DNHS cohort. Adjustment for GC treatment and population stratification appears crucial in assessing genetic modifiers in DMD.
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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.