Genetic modifiers of ambulation in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study.
Bottom Line: Median ages at LoA were compared by Kaplan-Meier analysis and log-rank test.Cox regression confirmed a significant effect of SPP1 genotype in GC-treated participants (hazard ratio = 1.61, p = 0.016).After controlling for population stratification, we confirmed a strong effect of LTBP4 genotype in Caucasians (2.4 years, p = 0.024).
Affiliation: Children's National Medical Center, Washington, DC; Department of Neuroscience (Neurological, Psychiatric, Sensory, Reconstructive, Rehabilitative Science), University of Padua, Padua, Italy.Show MeSH
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Mentions: Analyses relative to SPP1 and LTBP4 genotypes were limited to 283 patients with available genomic DNA samples (see Fig 1). Of these, 279 (because of limited availability of genomic DNA for a few participants) were successfully genotyped for SPP1 rs28357094. Median ages at LoA for genotype groups and results of log-rank and Cox regression analyses are summarized in Table3. Median ages at LoA were 11.8 years in 84 participants carrying the minor allele (TG/GG), and 13.0 years in 195 participants carrying the TT genotype (log-rank p = 0.048, Fig 2A). This closely reproduces the methodology of the previously reported association of rs28357094 genotype with LoA in 106 Italian patients,4 representing an independent validation of association with this phenotype. In the Cox regression model with GC treatment as time-varying covariate, the hazard ratio (HR) ± SE for TG/GG genotype was 1.22 ± 0.20 (p = nonsignificant [n.s.]). The HR for GC treatment was 0.41 ± 0.07 (p < 0.001).
Affiliation: Children's National Medical Center, Washington, DC; Department of Neuroscience (Neurological, Psychiatric, Sensory, Reconstructive, Rehabilitative Science), University of Padua, Padua, Italy.