Exploring Genetic Factors in Vitiligo and AA

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Vitiligo, while not life-threatening, can severely affect patients’ physical and mental health, as well as their quality of life.¹ The pathogenesis of vitiligo remains complex and multifaceted, involving autoimmune, neuroendocrine, oxidative stress (OS), genetic, and environmental factors, with current treatments often proving inadequate and burdensome.² Similarly, emotional burdens faced by patients with alopecia areata (AA) include a loss of self-esteem, emotional distress, and disruptions in various aspects of life such as school, work, relationships, and mood.³ The exact mechanisms behind AA are also unclear, but genetic susceptibility and autoimmune processes play roles.⁴ Emerging research highlights OS as a significant factor in the pathogenesis of both conditions, influencing disease progression and response to treatment.⁵

Researchers behind a recent study aimed to investigate the role of OS and common genetic factors in vitiligo and AA through bioinformatics analysis, providing insights that could enhance understanding and management of these challenging disorders.⁶

“OS is the common pathogenesis of these 2 diseases. KLB and EIF3C play a crucial role in the progression and development of vitiligo and AA, which have been identified as a biomarker and target for early diagnosis of patients,” researchers behind the study wrote.

Data Collection

Two datasets (GSE65127 and GSE68801) were taken from the gene expression omnibus database. Researchers stated that the GSE65127 sample consisted of samples from 30 patients with vitiligo and 10 healthy controls with platforms GPL570, the GSE68801 sample consisted of samples from 86 patients with AA and 36 healthy controls with platforms GPL570.

Results

Researchers identified the relevant differential genes through the analysis of vitiligo and AA datasets, visualizing the top 10 genes using a heat map. They stated a total of 565 up-regulated genes and 98 down-regulated genes were identified in AA dataset, while 85 up-regulated genes and 117 down-regulated genes were identified in the vitiligo dataset.

The study utilized gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enriched analyses to explore the molecular pathways associated with vitiligo and AA. In vitiligo, significant enrichment was observed in pathways related to phenol-containing compounds, melanosome function, and pigment granules, with key pathways including melanogenesis. Conversely, researchers found AA showed enrichment in epidermis development, intermediate filament structures, and receptor agonist activity, with notable pathways being cytokine−cytokine receptor interaction. Gene set enrichment analysis (GSEA) revealed to researchers that vitiligo is associated with cell cycle, proteasome function, and ubiquitin-mediated proteolysis, while AA is linked to cell adhesion, chemokine signaling, and toll-like receptor pathways.

Additionally, researchers identified 2 potential biomarkers, KLB and EIF3C, through VEEN package analysis, which were further validated with ROC curves showing promising diagnostic accuracy for both conditions. In vitiligo, EIF3C and KLB had AUC values of 0.775 and 0.825, respectively, while in AA, the values were 0.716 and 0.708. The study stated immune cell infiltration analysis revealed no significant differences in immune cells between vitiligo and controls, but AA exhibited notable T cell and M2 macrophage activity. EIF3C and KLB's interactions with immune cells were also examined, revealing their roles in regulating various T cell subsets and neutrophils across both conditions.

Conclusion

The study found that OS emerged as a common underlying mechanism in both vitiligo and AA, influencing the progression and severity of these autoimmune skin diseases. Researchers highlighted KLB and EIF3C as significant biomarkers, which could assist in early diagnosis of patients and the development of more effective, targeted therapies for vitiligo and AA.

References

1. Crummer E, Cohen JT, Rosmarin D, et al. Impact on quality of life, health care access, and health care utilization of individuals with vitiligo: an analysis of the All of Us research program. Arch Dermatol Res. 2024;316(8):554. Published 2024 Aug 22. doi:10.1007/s00403-024-03275-8
2. Bergqvist C, Ezzedine K. Vitiligo: A Review. Dermatology. 2020;236(6):571-592. doi:10.1159/000506103
3. Buchanan L. Alopecia areata: A comprehensive overview and breakthrough therapies. Dermatology Times. Published February 17, 2024. Accessed August 29, 2024. https://www.dermatologytimes.com/view/alopecia-areata-a-comprehensive-overview-and-breakthrough-therapies
4. Gill L, Zarbo A, Isedeh P, Jacobsen G, et al. Comorbid autoimmune diseases in patients with vitiligo: A cross-sectional study. J Am Acad Dermatol. 2016;74(2):295-302. doi:10.1016/j.jaad.2015.08.063
5. Smallwood MJ, Nissim A, Knight AR, et al. Oxidative stress in autoimmune rheumatic diseases. Free Radic Biol Med. 2018;125:3-14. doi:10.1016/j.freeradbiomed.2018.05.086
6. Sun C, Ding H, Zhang L, et al. Co-regulatory mechanisms and potential markers of oxidative stress-related genes in vitiligo and alopecia areata. Skin Res Technol. 2024;30(8):e70001. doi:10.1111/srt.70001