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

TITLE=Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00721

DOI=10.3389/fneur.2020.00721

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> 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 <italic>SPP1</italic> and <italic>LTBP4</italic> on DMD progression in Chinese patients.</p><p><bold>Methods:</bold> We genotyped <italic>LTBP4</italic> haplotypes and the <italic>SPP1</italic> 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, <italic>DMD</italic> genotype, and <italic>SPP1</italic>/<italic>LTBP4</italic> SNPs on loss of ambulation.</p><p><bold>Results:</bold> The CC/CT genotype at rs11730582 was associated with a 1.33-year delay in ambulation loss (<italic>p</italic> = 0.006), with hazard ratio 0.63 (<italic>p</italic> = 0.008), in patients with truncated <italic>DMD</italic> genotype and undergoing steroid treatment. On the other hand, rs17524488 in <italic>SPP1</italic> and the IAAM/IAAM haplotype in <italic>LTBP4</italic> were not associated with time to ambulation loss.</p><p><bold>Conclusions:</bold><italic>SPP1</italic> 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, <italic>DMD</italic> genotype, and <italic>SPP1</italic> polymorphisms.</p>