Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients

Menglong Chen; Liang Wang; Yaqin Li; Yongjun Chen; Huili Zhang; Yuling Zhu; Ruojie He; Huan Li; Jinfu Lin; Yu Zhang; Cheng Zhang

doi:10.3389/fneur.2020.00721

Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients

Front Neurol. 2020 Jul 29:11:721. doi: 10.3389/fneur.2020.00721. eCollection 2020.

Authors

Menglong Chen^{1

2

3}, Liang Wang¹, Yaqin Li⁴, Yongjun Chen⁵, Huili Zhang⁶, Yuling Zhu¹, Ruojie He¹, Huan Li¹, Jinfu Lin¹, Yu Zhang³, Cheng Zhang¹

Affiliations

¹ Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.
³ Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, China.
⁴ Department of Neurology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
⁵ Department of Neurology, Nanhua Hospital Affiliated to Nanhua University, Hengyang, China.
⁶ Department of Neurology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.

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; LTBP4; SPP1; genetic modifiers; single nucleotide polymorphisms.

Associated data

figshare/10.6084/m9.figshare.12421064