New Genetic Insights Into Alopecia Areata

Alopecia areata is linked to specific trace elements, serum metabolites, and inflammatory factors, according to a genetic analysis, suggesting potential new treatment and prevention strategies. | Image Credit: Yurii Kibalnik - stock.adobe.com

Alopecia areata has a genetic relationship with trace elements, serum metabolites, and inflammatory factors that highlights the potential value of targeted therapeutic strategies and preventive measures, according to a study published in Skin Research and Technology.¹

Genetics, environmental factors, and immune dysregulation influence alopecia areata development. There is an increased risk between alopecia areata and atopy and allergies such as hay fever, eczema, asthma, and allergies to pollen, dust, and cats.² Hypothyroidism has also been found to contribute to the development of alopecia areata among patients.³ Currently, there is little research that explores the association between developing alopecia areata and the progression of trace elements, serum modalities, and inflammatory cytokines that could be influencing the onset of the disease.¹

Trace elements are essential building blocks for cells that play a crucial role in processes like energy production, tissue repair, and nerve function. They help maintain the balance of immune cells, which is vital for preventing autoimmune diseases. Fluctuations in trace element levels can disrupt these functions and potentially contribute to the development of autoimmune conditions.

Serum metabolites serve as biomarkers of metabolic activity, reflecting the alterations in metabolic pathways associated with disease states. Monitoring these metabolites in alopecia areata can provide a better understanding of the metabolic underpinnings of the disease and how it will evolve over time.

Monocytes, a type of immune cell, may play a role in the development of alopecia areata but understanding the connection between these cells could help us better understand the causes of the disease and develop new treatments.

A Mendelian randomization analysis was conducted to genetically confirm the link between trace elements, metabolites, and inflammatory markers with the risk of alopecia areata. This study aimed to identify novel biological pathways and potential therapeutic targets.

The study examined 15 common trace elements and a total of 198 single nucleotide polymorphisms were labeled as inverse variance weighted (IVW). The IVW analysis highlights the possible connection between copper levels and the risk of developing alopecia areata (OR, 0.86; 95% CI, 0.75-0.99; P = .041). No heterogeneity was revealed (P = .922) and there was no evidence of horizontal pleiotropy detected (P = .749).

There was an inverse correlation between alopecia areata development and the levels of Gamma-glutamylglutamine (OR, 0.35; 95% CI, 0.16-0.76; P = .007), X-12707 (OR, 0.55; 95% CI, 0.32-0.93; P = .026), and (N(1) + N (8))-acetylspermidine (OR, 0.61; 95% CI, 0.41-0.91; P = .015). Alopecia areata risk also has possible positive correlations with levels of N-acetylarginine (OR, 1.31; 95% CI, 1.03-1.65; P = .025) and 12 additional serum metabolites.

Inflammatory factors with an inverse correlation to an increased risk of alopecia areata development included levels of C-C motif chemokine 23 (OR, 0.56; 95% CI, 0.39-0.81; P = .001), monocyte chemoattractant protein-3 (OR, 0.64; 95% CI, 0.42-0.97; P = .035), and Cystatin D (OR, 0.78; 95% CI, 0.61-0.99; P = .042).

Additional positive correlations with alopecia areata risk were found in transforming growth factor-alpha (OR, 1.72; 95% CI, 1.01-2.94; P = .044), interleukin-2 receptor subunit beta (OR, 1.80; 95% CI, 1.01-3.19; P = .044), and interferon gamma (OR, 2.23; 95% CI, 1.34-3.71; P = .001).

One of the limitations is the study design because it relies on the effectiveness of genetic tools and may not consider all relevant biological pathways, the authors noted. The largely European population included in the study limits the results to specific ethnicities and geographical locations. Overall data interpretation is limited because the casual mechanism between alopecia areata risk and some biomarkers remains unclear.

Higher levels of copper were found to be casually associated with a reduced risk of alopecia areata, suggesting its potential protective effect against autoimmune hair loss. Conversely, elevated levels of specific inflammatory markers were linked to a higher risk of hair follicle damage, highlighting the importance of further research to better understand the underlying mechanisms of alopecia areata.

References

1. Peng S, Yang Y, Man Y, et al. Explore the genetic exposure to alopecia areata. Skin Res Technol. 2024;30(8):e13874. doi:10.1111/srt.13874
2. Santoro C. Alopecia areata risk associated with atopy, allergies. AJMC^®. May 13, 2024. Accessed October 14, 2024. https://www.ajmc.com/view/alopecia-areata-risk-associated-with-atopy-allergies
3. Kaltwasser J. Alopecia areata linked with hypothyroidism. AJMC. October 2, 2024. Accessed October 14, 2024. https://www.ajmc.com/view/alopecia-areata-linked-with-hypothyroidism