October 29, 2015PLoS ONEOpen Access

Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Duchenne muscular dystrophy (n=178). Intervention: LTBP4 rs10880 and SPP1 rs28357094 polymorphisms vs. Alternative genotypes at the same loci. Primary outcome: Age at onset of dilated cardiomyopathy (DCM), defined as left ventricular ejection fraction 70 mL/m2 (p=0.027).

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Key result

The recessive T allele at LTBP4 rs10880 was associated with a significant delay in the onset of dilated cardiomyopathy among steroid-treated patients with Duchenne muscular dystrophy (log-rank p=0.027).

Why the study?

Do SPP1 and LTBP4 genetic polymorphisms modify the age of onset of dilated cardiomyopathy in patients with Duchenne muscular dystrophy?

Population

178 patients with confirmed Duchenne muscular dystrophy with regular cardiologic follow-up and available DNA…

Comparison

Genetic polymorphisms SPP1 rs28357094 and LTBP4… vs Alternative alleles/genotypes of the same…

Design

Cohort

Follow-up

average age of 15.9 ± 6.7 years

Authors

ABAndrea BarpCentro Clinico Nemo LBLuca BelloUniversity of Padua LPLuisa PolitanoUniversity of Campania "Luigi Vanvitelli"

Discussion

Member takes

Implication

Hypothesis-generating for LTBP4-guided risk stratification in DMD; requires prospective validation before clinical adoption.

Study Design

Type

Cohort (n=178)

Multicenter

Yes

Structured PICO

Do SPP1 and LTBP4 genetic polymorphisms modify the age of onset of dilated cardiomyopathy in patients with Duchenne muscular dystrophy?

Population

178 male patients with Duchenne muscular dystrophy and regular cardiologic follow-up, followed to an average age of 15.9 years to evaluate genetic modifiers of dilated cardiomyopathy.

Exposure

Genetic polymorphisms SPP1 rs28357094 and LTBP4 rs10880/haplotypes

Comparator

Alternative alleles/genotypes of the same polymorphisms

Outcome

Age at onset of dilated cardiomyopathy (DCM), defined as first echocardiographic finding of LV ejection fraction < 50% and/or end diastolic volume > 70 mL/m2surrogate

Main Result

p-value: p=0.027

Genetic modifiers such as LTBP4 polymorphisms may have a protective effect on the development of dilated cardiomyopathy in Duchenne muscular dystrophy, particularly in steroid-treated patients.

Limitations

Retrospective study design
Only one of LV-EF or LV-EDV was available for some patients
Age at DCM onset does not necessarily correlate with progression towards heart failure
Treatment and follow-up were not standardized across the multicentric cohort
only one of LV-EF or LV-EDV were available for some patients
age at DCM onset does not necessarily correlate with progression towards heart failure
treatment and follow-up were not standardized in this retrospective, multicentric study

Cite This Study

Barp et al. (2015) conducted a cohort in Duchenne muscular dystrophy (n=178). LTBP4 rs10880 and SPP1 rs28357094 polymorphisms vs. Alternative genotypes at the same loci was evaluated on Age at onset of dilated cardiomyopathy (DCM), defined as left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m2 (p=0.027). The recessive T allele at LTBP4 rs10880 was associated with a significant delay in the onset of dilated cardiomyopathy among steroid-treated patients with Duchenne muscular dystrophy (log-rank p=0.027).

synapsesocial.com/papers/6a73178acdd331ef01acb610 https://doi.org/10.1371/journal.pone.0141240

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Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy

Discussion

Member takes

Implication

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy

Discussion

Member takes

Implication

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider