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CD40 variant identified as modifier in Duchenne's muscular dystrophy

A variant on the CD40 gene was identified as a modifier locus of Duchenne’s muscular dystrophy, according to findings published in the American Journal of Human Genetics.

“If you have [Duchenne’s muscular dystrophy], and you carry a common genetic variant, [that is] a single nucleotide polymorphism in the CD40 gene, you will have faster progression of muscle weakness, and are at risk of losing ambulation earlier — around 1 year on average,” Luca Bello, MD, of the Center for Genetic Research, Children’s National Medical Center in Washington, D.C., told Healio Family Medicine.

Luca Bello

Bello and colleagues evaluated whether genetic components were associated with age at loss of ambulation in a cohort of patients with Duchenne’s muscular dystrophy. They performed genotyping on a cohort of patients with European or European-American ancestry (n = 109) from the Cooperative International Research Group Duchenne Natural History Study. They focused on 438 single nucleotide polymorphisms (SNPs) on 384 genes previously implicated in Duchenne’s muscular dystrophy.

They identified a minor allele, rs1883832, on the CD40 gene that was associated with earlier loss of ambulation. According to the researchers, this allele, “diminishes the expression of CD40, a co-stimulatory molecule for T cell polarization.”

The researchers validated the findings in three additional independent cohorts: the Padova Duchenne’s muscular dystrophy cohort (n = 95) that showed a 0.3 year earlier average loss of ambulation; the United Dystrophinopathy Project cohort (n = 243), that showed a 0.5 year earlier average loss of ambulation; and the BIO-NMD cohort (n = 246) that showed a 0.6 year earlier average loss of ambulation.

“We think that none of the three [Duchenne’s muscular dystrophy] genetic modifiers described so far — SPP1, LTBP4, and CD40 — should be used as a prognostic factor by itself, as so many other factors are at play, and the predictive power of genotyping one SNP in one patient is very small,” Bello said. “However, we think that we have added one more piece to the puzzle of understanding how the genetic background influences the disease course of [Duchenne’s muscular dystrophy], and we hope this will eventually lead to an improved, ‘precision medicine’ approach to [Duchenne’s muscular dystrophy] care.” – by Janel Miller

Disclosure: Healio Family Medicine was unable to determine researchers’ relevant financial disclosures prior to publication.