, , and Variants: Genetic Modifiers of Duchenne Muscular Dystrophy Analyzed in Serbian Patients.

Background: Clinical course variability in Duchenne muscular dystrophy (DMD) is partially explained by the mutation location in the gene and variants in modifier genes. We assessed the effect of the , , and genes and mutation location on loss of ambulation (LoA).

Methods: SNPs in -rs28357094, -rs2303729, rs1131620, rs1051303, rs10880, and -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 ( = 0.04). The modifying effect of and variants, as well as 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 haplotype and statistically significantly fewer genotypes with harmful T allele and "distal" DMD mutations.

Conclusions: The modifying effect of , , and was not replicated in Serbian patients, although our cohort was comparable in terms of its 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.