학술논문

Genetic modifiers of ambulation in the cooperative international Neuromuscular research group Duchenne natural history study
Document Type
article
Source
Annals of Neurology. 77(4)
Subject
Biomedical and Clinical Sciences
Neurosciences
Clinical Sciences
Genetics
Intellectual and Developmental Disabilities (IDD)
Pediatric
Muscular Dystrophy
Human Genome
Rare Diseases
Clinical Research
Brain Disorders
Clinical Trials and Supportive Activities
Adolescent
Adult
Child
Child
Preschool
Cohort Studies
Ethnicity
Humans
International Cooperation
Latent TGF-beta Binding Proteins
Male
Mobility Limitation
Muscular Dystrophy
Duchenne
Osteopontin
Walking
Young Adult
Cooperative International Neuromuscular Research Group Investigators
Neurology & Neurosurgery
Clinical sciences
Language
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,