DNA methylation patterns associated with oxidative stress in an ageing population

Area of Science:

• Epigenetics
• Metabolomics
• Genomics

Background:

• Oxidative stress is linked to type 2 diabetes (T2D) and cardiovascular disease (CVD).
• Epigenetic modifications, such as DNA methylation, may mediate the effects of environmental factors like oxidative stress on complex diseases.
• Understanding these epigenetic links can reveal new genes and mechanisms involved in disease development.

Purpose of the Study:

• To investigate the role of genome-wide DNA methylation in oxidative stress marker levels.
• To examine the association between epigenetic variation, oxidative stress, and the incidence of CVD and T2D.

Main Methods:

• Genome-wide DNA methylation analysis was performed on blood samples from up to 966 individuals.
• Ten markers of oxidative stress were measured, including glutathione, homocysteine, and oxidized LDL.
• Incident CVD and T2D events were tracked over a 10-year follow-up period.

Main Results:

• 66 cytosine-guanine (CpG) sites were significantly associated with oxidative stress markers, enriched in genomic regulatory regions.
• CpG sites in HIST1H4D and DVL1 were associated with incident T2D, suggesting a role in diabetes development or progression.
• Methylation QTL (meQTL) analysis identified genetic variants influencing DNA methylation at 42% of the oxidative stress-associated sites.

Conclusions:

• Novel associations between DNA methylation and oxidative stress markers were identified.
• Some of these DNA methylation sites also showed a relationship with the incidence of type 2 diabetes.
• Epigenetic regulation is implicated in the processes linking oxidative stress to T2D development.