Longitudinal leucocyte DNA methylation changes in Mesoamerican nephropathy

Area of Science:

• Environmental Epigenetics
• Nephrology
• Biomarker Discovery

Background:

• Mesoamerican nephropathy (MeN) is a significant health issue in Central America with an unknown cause.
• Environmental factors like heat, pesticides, and heavy metals are suspected contributors.
• DNA methylation (DNAm) changes, measurable in blood, could serve as biomarkers for environmental exposures.

Purpose of the Study:

• To identify disease-specific DNA methylation signatures for MeN using an epigenome-wide association study.
• To investigate associations between DNA methylation changes and environmental exposures linked to MeN onset.

Main Methods:

• Whole-blood epigenome-wide DNA methylation analysis was performed on 312 samples (53 incident cases, 61 controls, 16 established cases) over 5 years.
• Mixed-effect models were used to identify differentially methylated regions associated with incident kidney injury.
• A hypothesis-driven analysis examined CpG sites linked to temperature, pesticides, arsenic, cadmium, and chromium.

Main Results:

• Three unique differentially methylated regions were associated with incident kidney injury, with two located within gene introns (Amphiphysin and SLC29A3).
• No significant associations were found between DNA methylation patterns and exposure to ambient temperature, pesticides, arsenic, cadmium, or chromium.
• Previously reported DNA methylation patterns supporting a role for these environmental factors in MeN were not observed.

Conclusions:

• This study identified novel DNA methylation signatures associated with incident kidney injury in MeN.
• The findings do not support a direct role for the investigated environmental exposures (pesticides, metals, temperature) in MeN etiology via the studied DNA methylation pathways.
• Further research is needed to elucidate the complex etiology of Mesoamerican nephropathy.