Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients
Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients
复制标题
中国患者杜氏肌营养不良症的基因修饰
DOI：
10.3389/fneur.2020.00721
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发表时间：
2020-07-29
影响因子：
3.4
通讯作者：
Zhang, Cheng
中科院分区：
文献类型：
--
作者：
Chen, Menglong;Wang, Liang;Zhang, Cheng
背景：杜氏肌营养不良症 (DMD) 是一种致命的 X 连锁隐性肌肉疾病，其特征是进展和严重程度不均。我们的目的是研究 SPP1 和 LTBP4 中的单核苷酸多态性 (SNP) 对中国患者 DMD 进展的影响。方法：我们对中山大学附属第一医院神经肌肉数据库中登记的326例患者的LTBP4单倍型和SPP1启动子SNP rs28357094、rs11730582和rs17524488进行基因分型。 Kaplan-Meier 曲线和对数秩检验用于估计和比较丧失行走能力时的中位年龄，而 Cox 比例风险回归模型用于分析糖皮质激素治疗、DMD 基因型和 SPP1/LTBP4 SNP 对行走能力丧失的影响。结果：在 DMD 基因型截短并接受类固醇治疗的患者中，rs11730582 的 CC/CT 基因型与行走丧失延迟 1.33 年相关（p = 0.006），风险比为 0.63（p = 0.008）。另一方面，SPP1 中的 rs17524488 和 LTBP4 中的 IAAM/IAAM 单倍型与步行时间丧失无关。结论：SPP1 rs11730582 是中国 DMD 患者类固醇治疗长期效果的遗传修饰因子。因此，任何未来的 DMD 临床研究都应根据糖皮质激素的使用、DMD 基因型和 SPP1 多态性进行调整。
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.