^{Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China}

^{Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, China}

^{Department of Neurology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China}

^{Department of Neurology, Nanhua Hospital Affiliated to Nanhua University, Hengyang, China}

^{Department of Neurology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China}

Edited by: Edoardo Malfatti, INSERM U1179 Handicap neuromusculaire: Physiopathologie, Biothérapie et Pharmacologie appliquées (END-ICAP), France

Reviewed by: Gerald Pfeffer, University of Calgary, Canada; Susan T. Iannaccone, University of Texas Southwestern Medical Center, United States

*Correspondence: Yu Zhang nc.ude.unj@6102gnahzuy

Cheng Zhang moc.liamtoh@001gnahzgnehc

This article was submitted to Neuromuscular Diseases, a section of the journal Frontiers in Neurology

†These authors share first authorship

Edited by: Edoardo Malfatti, INSERM U1179 Handicap neuromusculaire: Physiopathologie, Biothérapie et Pharmacologie appliquées (END-ICAP), France

Reviewed by: Gerald Pfeffer, University of Calgary, Canada; Susan T. Iannaccone, University of Texas Southwestern Medical Center, United States

Received 2020 Jan 21; Accepted 2020 Jun 15.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Background: Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive muscle disorder characterized by heterogeneous progression and severity. We aimed to study the effects of single nucleotide polymorphisms (SNPs) in SPP1 and LTBP4 on DMD progression in Chinese patients.

Methods: We genotyped LTBP4 haplotypes and the SPP1 promoter SNPs rs28357094, rs11730582, and rs17524488 in 326 patients registered in the neuromuscular database of The First Affiliated Hospital of Sun Yat-sen University. Kaplan-Meier curves and log-rank tests were used to estimate and compare median age at loss of ambulation, while Cox proportional hazard regression models were used as to analyze the effects of glucocorticoids treatments, DMD genotype, and SPP1/LTBP4 SNPs on loss of ambulation.

Results: The CC/CT genotype at rs11730582 was associated with a 1.33-year delay in ambulation loss (p = 0.006), with hazard ratio 0.63 (p = 0.008), in patients with truncated DMD genotype and undergoing steroid treatment. On the other hand, rs17524488 in SPP1 and the IAAM/IAAM haplotype in LTBP4 were not associated with time to ambulation loss.

Conclusions:SPP1 rs11730582 is a genetic modifier of the long-term effects of steroid treatment in Chinese DMD patients. Thus, any future clinical study in DMD should adjust for glucocorticoids use, DMD genotype, and SPP1 polymorphisms.

Keywords: Duchenne muscular dystrophy, genetic modifiers, single nucleotide polymorphisms, SPP1, LTBP4

Abstract

Acknowledgments

The authors thank all individuals for their participation. We would like to thank Editage [www.editage.cn] for English language editing.

Acknowledgments

Footnotes

Funding. The study was funded by the National Natural Science Foundation of China (Grant Nos. 81901280, 81771359, 81801246, and 81471280), the Guangdong Provincial Science and Technology Plan (2017A020215094), the Natural Science Foundation of Guangdong Province (2018A030313636), the Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases (2015B050501003), Guangdong Provincial Engineering Center For Major Neurological Disease Treatment, Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease, and Guangdong Provincial Clinical Research Center for Neurological Diseases.

Footnotes

Click here for additional data file.^{(36K, DOC)}Click here for additional data file.^{(42K, DOC)}Click here for additional data file.^{(41K, DOC)}Click here for additional data file.^{(32K, XLSX)}

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