Key result
The LTBP4 haplotype IAAM was associated with a protective effect against loss of ambulation in patients with Duchenne muscular dystrophy (HR 0.78; 95% CI 0.67-0.90).
Why the study?
The transforming growth factor beta (TGFβ) pathway could modulate the Duchenne muscular dystrophy phenotype, prompting evaluation of its genetic variants' association with age of loss of ambulation and cardiac function.
Do genetic variants in the TGFβ pathway (LTBP4 and SPP1) modify the age of loss of ambulation and cardiac function in patients with Duchenne muscular dystrophy?
Meta-Analysis
Do genetic variants in the TGFβ pathway (LTBP4 and SPP1) modify the age of loss of ambulation and cardiac function in patients with Duchenne muscular dystrophy?
The LTBP4 haplotype IAAM is associated with a later loss of ambulation in patients with Duchenne muscular dystrophy, suggesting it acts as a protective genetic modifier.
May refine ambulation prognosis in Caucasian DMD without altering care; confirms LTBP4 as a modifier while leaving SPP1-steroid and cardiac effects open.
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 (LTBP4) and secreted phosphoprotein 1 (SPP1) 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 LTBP4 haplotype IAAM (recessive model) for LoA. It is also suggested that the SPP1 rs28357094 genotype G (dominant model) is associated with early LoA in glucocorticoids-treated patients. The meta-analysis of the LTBP4 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 SPP1 rs28357094. The LTBP4 haplotype IAAM is associated with a later LoA, especially in the Caucasian population, while the SPP1 rs28357094 genotype G could be associated with a poor response to glucocorticoids. Future research is suggested for SPP1 rs11730582, LTBP4 rs710160, and THBS1 rs2725797.
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Pascual‐Morena et al. (2021) conducted a meta-analysis in Duchenne muscular dystrophy (DMD). LTBP4 haplotype IAAM vs. Other haplotypes was evaluated on Loss of ambulation (LoA) (HR 0.78, 95% CI 0.67-0.90). The LTBP4 haplotype IAAM was associated with a protective effect against loss of ambulation in patients with Duchenne muscular dystrophy (HR 0.78; 95% CI 0.67-0.90).
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