Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients

Abstract

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