Background: Clinical course variability in Duchenne muscular dystrophy (DMD) is partially explained by the mutation location in the
DMD gene and variants in modifier genes. We assessed the effect of the
SPP1,
CD40, and
LTBP4 genes and
DMD mutation location on
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Background: Clinical course variability in Duchenne muscular dystrophy (DMD) is partially explained by the mutation location in the
DMD gene and variants in modifier genes. We assessed the effect of the
SPP1,
CD40, and
LTBP4 genes and
DMD mutation location on loss of ambulation (LoA). Methods: SNPs in
SPP1-rs28357094,
LTBP4-rs2303729, rs1131620, rs1051303, rs10880, and
CD40-rs1883832 were genotyped, and their effect was assessed by survival and hierarchical cluster analysis. Results: Patients on glucocorticoid corticosteroid (GC) therapy experienced LoA one year later (
p = 0.04). The modifying effect of
SPP1 and
CD40 variants, as well as
LTBP4 haplotypes, was not observed using a log-rank test and multivariant Cox regression analysis. Cluster analysis revealed two subgroups with statistical trends in differences in age at LoA. Almost all patients in the cluster with later LoA had the protective IAAM
LTBP4 haplotype and statistically significantly fewer
CD40 genotypes with harmful T allele and “distal” DMD mutations. Conclusions: The modifying effect of
SPP1,
CD40, and
LTBP4 was not replicated in Serbian patients, although our cohort was comparable in terms of its
DMD mutation type distribution, SNP allele frequencies, and GC-positive effect with other European cohorts. Cluster analysis may be able to identify patient subgroups carrying a combination of the genetic variants that modify LoA.
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