Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis

• Main Authors: Carlos Pascual-Morena (Author), Iván Cavero-Redondo (Author), Alicia Saz-Lara (Author), Irene Sequí-Domínguez (Author), Maribel Lucerón- (Author), Vicente Martínez-Vizcaíno (Author)
• Format: Book
• Published: MDPI AG, 2021-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 (<i>LTBP4</i>) and secreted phosphoprotein 1 (<i>SPP1</i>) 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 <i>LTBP4</i> haplotype IAAM (recessive model) for LoA. It is also suggested that the <i>SPP1</i> rs28357094 genotype G (dominant model) is associated with early LoA in glucocorticoids-treated patients. The meta-analysis of the <i>LTBP4</i> 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 <i>SPP1</i> rs28357094. The <i>LTBP4</i> haplotype IAAM is associated with a later LoA, especially in the Caucasian population, while the <i>SPP1</i> rs28357094 genotype G could be associated with a poor response to glucocorticoids. Future research is suggested for <i>SPP1</i> rs11730582, <i>LTBP4</i> rs710160, and <i>THBS1</i> rs2725797.

Item Description

10.3390/ph14080798
1424-8247