DNA Methylation at cg18095732 Modulates ZDHHC20 Expression and Decreases Acne Vulgaris Risk

Area of Science:

• Genetics
• Epigenetics
• Dermatology

Background:

• Acne vulgaris is a chronic inflammatory skin condition influenced by lipid metabolism and immune responses.
• Protein S-palmitoylation impacts lipid homeostasis, and DNA methylation is implicated in acne development.
• The interplay between DNA methylation and palmitoylation in acne pathogenesis is not well understood.

Purpose of the Study:

• To investigate the causal relationship between palmitoylation-related genes and acne risk.
• To integrate genetic and epigenetic data using Mendelian randomization (MR) and other analyses.
• To explore the specific roles of DNA methylation and palmitoylation in acne.

Main Methods:

• Utilized Mendelian randomization (MR) and Sampled-based Mendelian Randomization (SMR) analyses.
• Integrated large-scale genetic and epigenetic datasets.
• Performed mediation and sensitivity analyses to confirm findings and assess pleiotropy/heterogeneity.

Main Results:

• Identified ZDHHC20, a palmitoyltransferase gene, as significantly negatively associated with acne risk.
• Found that hypermethylation at CpG site cg18095732 positively correlated with ZDHHC20 expression.
• Demonstrated that cg18095732 methylation mediated 61.90% of the effect, reducing acne risk.

Conclusions:

• Established a regulatory pathway where DNA methylation at cg18095732 up-regulates ZDHHC20, lowering acne susceptibility.
• Highlighted epigenetic regulation as a potential biomarker for acne.
• Suggested epigenetic modifications as possible intervention points for inflammatory skin conditions.