Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients.

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) inSPP1andLTBP4on DMD progression in Chinese patients. Methods:We genotypedLTBP4haplotypes and theSPP1promoter 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,DMDgenotype, andSPP1/LTBP4SNPs 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 truncatedDMDgenotype and undergoing steroid treatment. On the other hand, rs17524488 inSPP1and the IAAM/IAAM haplotype inLTBP4were not associated with time to ambulation loss. Conclusions:SPP1rs11730582 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,DMDgenotype, andSPP1polymorphisms.