Pascual-Morena Carlos, Cavero-Redondo Iván, Saz-Lara Alicia, Sequí-Domínguez Irene, Lucerón-Lucas-Torres Maribel, Martínez-Vizcaíno Vicente
Health and Social Research Center, Universidad de Castilla-La Mancha, 16071 Cuenca, Spain.
Rehabilitation in Health Research Center (CIRES), Universidad de las Américas, Santiago 72819, Chile.
Pharmaceuticals (Basel). 2021 Aug 13;14(8):798. doi: 10.3390/ph14080798.
The transforming growth factor beta (TGFβ) pathway could modulate the Duchenne muscular dystrophy (DMD) phenotype. This meta-analysis aims to estimate the association of genetic variants involved in the TGFβ pathway, including the latent transforming growth factor beta binding protein 4 () and secreted phosphoprotein 1 () genes, among others, with age of loss of ambulation (LoA) and cardiac function in patients with DMD. Meta-analyses were conducted for the hazard ratio (HR) of LoA for each genetic variant. A subgroup analysis was performed in patients treated exclusively with glucocorticoids. Eight studies were included in the systematic review and four in the meta-analyses. The systematic review suggests a protective effect of haplotype IAAM (recessive model) for LoA. It is also suggested that the rs28357094 genotype G (dominant model) is associated with early LoA in glucocorticoids-treated patients. The meta-analysis of the haplotype IAAM showed a protective association with LoA, with an HR = 0.78 (95% CI: 0.67-0.90). No association with LoA was observed for the rs28357094. The haplotype IAAM is associated with a later LoA, especially in the Caucasian population, while the rs28357094 genotype G could be associated with a poor response to glucocorticoids. Future research is suggested for rs11730582, rs710160, and rs2725797.
转化生长因子β（TGFβ）通路可调节杜氏肌营养不良症（DMD）的表型。本荟萃分析旨在评估TGFβ通路中涉及的基因变异与DMD患者失步行走年龄（LoA）和心脏功能之间的关联，这些基因变异包括潜在转化生长因子β结合蛋白4（）和分泌磷蛋白1（）基因等。对每个基因变异的LoA风险比（HR）进行了荟萃分析。对仅接受糖皮质激素治疗的患者进行了亚组分析。系统评价纳入了8项研究，荟萃分析纳入了4项研究。系统评价表明，单倍型IAAM（隐性模型）对LoA有保护作用。还表明，rs28357094基因型G（显性模型）与糖皮质激素治疗患者的早期LoA相关。对单倍型IAAM的荟萃分析显示与LoA存在保护性关联，HR = 0.78（95%CI：0.67 - 0.90）。未观察到rs28357094与LoA有关联。单倍型IAAM与较晚的LoA相关，尤其是在白种人群中，而rs28357094基因型G可能与对糖皮质激素反应不佳有关。建议对rs11730582、rs710160和rs2725797进行进一步研究。
