The Role of the Major Histocompatibility Complex Region on Chromosome 6 in Skin Atrophy: A Mendelian Randomization Study

• DOI: 10.1111/jocd.70040
• Publication Date: 2025-03-18T08:35:46Z
• Authors: Chenyu Zhao; Zhonghao Fan; Ruihan Zhang; Yuehang Sun; Wen‐Yang Li
• Keywords: Genome-wide Association Study

Skin atrophy (SA) is a pathological condition marked by the thinning of skin, decreased elasticity, and reduced functionality, often arising from aging, chronic glucocorticoid use, or autoimmune diseases. This study investigates role major histocompatibility complex (MHC) region on chromosome 6 in development SA. We applied summary-data-based Mendelian randomization (SMR) using eQTL data three skin-related tissues (whole blood, lower leg, suprapubic) GTEx database, SA genome-wide association FinnGen. Further, we conducted functional enrichment, colocalization, drug enrichment analyses core genes (intersection genes) to explore their functions druggability. Six (PSORS1C3, HLA-C, HLA-DRB5, HLA-DRB6, HLA-DQA1, HLA-DQB1) located 6p21 were consistently identified across all tissues. Functional pathway, protein-protein interaction revealed that these are involved antigen processing immune response regulation. Drug analysis highlighted potential therapeutic targets, including interactions with palladium, azathioprine, insulin. However, limitations available for PSORS1C3 as well inconclusive colocalization results, suggest need further research. highlights involvement six within MHC SA, emphasizing roles regulation presentation. These findings open new avenues understanding offer foundation future investigations into immune-related pathways skin