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

IF 2.3 4区医学 Q2 DERMATOLOGY Journal of Cosmetic Dermatology Pub Date : 2025-03-18 DOI:10.1111/jocd.70040

Chenyu Zhao, Zhonghao Fan, Ruihan Zhang, Yuehang Sun, Wen-Yang Li

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Abstract

Background

Skin atrophy (SA) is a pathological condition marked by the thinning of the skin, decreased elasticity, and reduced functionality, often arising from aging, chronic glucocorticoid use, or autoimmune diseases.

Objective

This study investigates the role of the major histocompatibility complex (MHC) region on chromosome 6 in the development of SA.

Methods

We applied summary-data-based Mendelian randomization (SMR) using eQTL data of three skin-related tissues (whole blood, lower leg, and suprapubic) from the GTEx database, and SA genome-wide association study data from FinnGen. Further, we conducted functional enrichment, colocalization, and drug enrichment analyses on the core genes (intersection genes) to explore their functions and druggability.

Results

Six core genes (PSORS1C3, HLA-C, HLA-DRB5, HLA-DRB6, HLA-DQA1, and HLA-DQB1) located on chromosome 6p21 were consistently identified across all tissues. Functional enrichment, pathway, and protein–protein interaction analyses revealed that these genes are involved in antigen processing and immune response regulation. Drug enrichment analysis highlighted potential therapeutic targets, including interactions with palladium, azathioprine, and insulin. However, limitations in available data for PSORS1C3 and HLA-DRB6, as well as inconclusive colocalization results, suggest a need for further research.

Conclusion

This study highlights the involvement of six core genes within the MHC region on chromosome 6 in the development of SA, emphasizing their roles in immune regulation and antigen presentation. These findings open new avenues for understanding SA and offer a foundation for future investigations into immune-related pathways in skin diseases.

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来源期刊

Journal of Cosmetic Dermatology DERMATOLOGY-

CiteScore

4.30

自引率

13.00%

发文量

818

审稿时长

>12 weeks

期刊介绍： The Journal of Cosmetic Dermatology publishes high quality, peer-reviewed articles on all aspects of cosmetic dermatology with the aim to foster the highest standards of patient care in cosmetic dermatology. Published quarterly, the Journal of Cosmetic Dermatology facilitates continuing professional development and provides a forum for the exchange of scientific research and innovative techniques. The scope of coverage includes, but will not be limited to: healthy skin; skin maintenance; ageing skin; photodamage and photoprotection; rejuvenation; biochemistry, endocrinology and neuroimmunology of healthy skin; imaging; skin measurement; quality of life; skin types; sensitive skin; rosacea and acne; sebum; sweat; fat; phlebology; hair conservation, restoration and removal; nails and nail surgery; pigment; psychological and medicolegal issues; retinoids; cosmetic chemistry; dermopharmacy; cosmeceuticals; toiletries; striae; cellulite; cosmetic dermatological surgery; blepharoplasty; liposuction; surgical complications; botulinum; fillers, peels and dermabrasion; local and tumescent anaesthesia; electrosurgery; lasers, including laser physics, laser research and safety, vascular lasers, pigment lasers, hair removal lasers, tattoo removal lasers, resurfacing lasers, dermal remodelling lasers and laser complications.