Sex-specific DNA methylation associations with circulating urate levels and BCG-induced urate changes

Area of Science:

• Epigenetics
• Human Physiology
• Sex Differences in Biology

Background:

• Serum urate homeostasis exhibits distinct sex differences.
• DNA methylation influences serum urate levels and cardiometabolic traits.
• The sex-specific relationship between DNA methylation and urate concentration remains unclear.

Purpose of the Study:

• To investigate the sex-specific associations between DNA methylation and serum urate concentrations.
• To explore if urate changes post-vaccination are linked to DNA methylation in a sex-specific manner.

Main Methods:

• Analysis of DNA methylation and serum urate in 325 healthy individuals before and after BCG vaccination.
• Utilized association, interaction, and sex-stratified analyses.
• BCG vaccination served as a perturbation to observe urate changes.

Main Results:

• Found 215 CpG sites associated with serum urate in males versus 5 in females, indicating sex-specific associations.
• Observed a significant increase in urate post-vaccination, with baseline DNA methylation correlating with urate changes sex-specifically.
• Male-associated CpG sites linked to neuroprotection; female-associated sites linked to lipid and glucose metabolism.

Conclusions:

• Epigenetic factors play a significant role in regulating serum urate levels in a sex-specific manner.
• Findings underscore the importance of personalized and sex-specific medical strategies.
• This research contributes to understanding the epigenetic basis of urate homeostasis.