Genome-wide methylation patterns in Marfan syndrome

Area of Science:

• Genetics
• Epigenetics
• Cardiovascular Diseases

Background:

• Marfan syndrome (MFS) is a genetic connective tissue disorder caused by Fibrillin-1 gene (FBN1) mutations.
• The genetic underpinnings and epigenetic modifications in MFS require further investigation.

Purpose of the Study:

• To conduct the first epigenome-wide association study (EWAS) in Marfan syndrome patients.
• To identify DNA methylation loci associated with MFS phenotypes, particularly aortic dimensions and clinical events.

Main Methods:

• Utilized the Illumina 450k DNA methylation array on peripheral whole-blood samples from 190 MFS patients.
• Performed genome-wide analysis to identify Differentially Methylated Positions (DMPs) and Regions (DMRs).
• Assessed associations between methylation levels and aortic diameters, clinical features, and adverse cardiovascular events.

Main Results:

• Identified 28 DMPs significantly associated with aortic diameters in MFS patients, with several linked to cardiovascular disease genes.
• Found DMPs associated with aortic diameter change and clinical events.
• Discovered novel involvement of protocadherins on chromosome 5 through DMR analysis.

Conclusions:

• This EWAS identified key methylation loci associated with aortic dimensions, dilatation rate, and events in Marfan syndrome.
• The findings contribute to understanding gene expression regulation in MFS.
• Highlights potential epigenetic markers for MFS progression and outcomes.