{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:32:34Z","timestamp":1790040754497,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T00:00:00Z","timestamp":1426204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH","award":["NICHD #U54HD053177"],"award-info":[{"award-number":["NICHD #U54HD053177"]}]},{"name":"NIH","award":["NICHD #R24HD050846"],"award-info":[{"award-number":["NICHD #R24HD050846"]}]},{"name":"NIH","award":["NCATS #UL1RR031988"],"award-info":[{"award-number":["NCATS #UL1RR031988"]}]},{"name":"NIH","award":["NCATS #UL1RR024992"],"award-info":[{"award-number":["NCATS #UL1RR024992"]}]},{"name":"NIH","award":["NCATS #U54RR026139"],"award-info":[{"award-number":["NCATS #U54RR026139"]}]},{"name":"NIH","award":["NCATS #G12RR003051"],"award-info":[{"award-number":["NCATS #G12RR003051"]}]},{"name":"NIH","award":["NIAMS #1R01AR061875"],"award-info":[{"award-number":["NIAMS #1R01AR061875"]}]},{"name":"NIH","award":["NIAMS #R01AR062380"],"award-info":[{"award-number":["NIAMS #R01AR062380"]}]},{"name":"US Department of Education\/National Institute on Disability and Rehabilitation Research","award":["#H133B031118, #H133B090001"],"award-info":[{"award-number":["#H133B031118, #H133B090001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We studied the effects of <jats:italic>LTBP4<\/jats:italic> and <jats:italic>SPP1<\/jats:italic> polymorphisms on age at loss of ambulation (LoA) in a multiethnic Duchenne muscular dystrophy (DMD) cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We genotyped <jats:italic>SPP1<\/jats:italic> rs28357094 and <jats:italic>LTBP4<\/jats:italic> haplotype in 283 of 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG\u2010DNHS). Median ages at LoA were compared by Kaplan\u2013Meier analysis and log\u2010rank test. We controlled polymorphism analyses for concurrent effects of glucocorticoid corticosteroid (GC) treatment (time\u2010varying Cox regression) and for population stratification (multidimensional scaling of genome\u2010wide markers).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hispanic and South Asian participants (n\u2009=\u200918, 41) lost ambulation 2.7 and 2 years earlier than Caucasian subjects (<jats:italic>p<\/jats:italic>\u2009=\u20090.003, &lt;0.001). The TG\/GG genotype at <jats:italic>SPP1<\/jats:italic> rs28357094 was associated to 1.2\u2010year\u2010earlier median LoA (<jats:italic>p<\/jats:italic>\u2009=\u20090.048). This difference was greater (1.9 years, <jats:italic>p<\/jats:italic>\u2009=\u20090.038) in GC\u2010treated participants, whereas no difference was observed in untreated subjects. Cox regression confirmed a significant effect of <jats:italic>SPP1<\/jats:italic> genotype in GC\u2010treated participants (hazard ratio\u2009=\u20091.61, <jats:italic>p<\/jats:italic>\u2009=\u20090.016). <jats:italic>LTBP4<\/jats:italic> 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 <jats:italic>LTBP4<\/jats:italic> genotype in Caucasians (2.4 years, <jats:italic>p<\/jats:italic>\u2009=\u20090.024). Median age at LoA with the protective <jats:italic>LTBP4<\/jats:italic> genotype in this cohort was 15.0 years, 16.0 for those who were treated with GC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p><jats:italic>SPP1<\/jats:italic> rs28357094 acts as a pharmacodynamic biomarker of GC response, and <jats:italic>LTBP4<\/jats:italic> haplotype modifies age at LoA in the CINRG\u2010DNHS cohort. Adjustment for GC treatment and population stratification appears crucial in assessing genetic modifiers in DMD. Ann Neurol 2015;77:684\u2013696<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24370","type":"journal-article","created":{"date-parts":[[2015,1,30]],"date-time":"2015-01-30T08:58:17Z","timestamp":1422608297000},"page":"684-696","source":"Crossref","is-referenced-by-count":107,"title":["Genetic modifiers of ambulation in the cooperative international Neuromuscular research group Duchenne natural history study"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-6525","authenticated-orcid":false,"given":"Luca","family":"Bello","sequence":"first","affiliation":[{"name":"Children's National Medical Center Washington DC"},{"name":"Department of Neuroscience (Neurological, Psychiatric, Sensory, Reconstructive, Rehabilitative Science) University of Padua Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akanchha","family":"Kesari","sequence":"additional","affiliation":[{"name":"Children's National Medical Center Washington 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