Genetic Changes in Psoriasis Patients Clear, but Carry Uncertain Consequences

Although there have been a lot of advances in the understanding of psoriasis over the last few decades, new research points not just to inflammation, but also to genetic changes in playing a role in the development and exacerbation of psoriasis vulgaris.

Psoriasis is a chronic inflammatory condition that produces dry, scaly patches on the skin. There are a few varieties of this condition, but psoriasis vulgaris is the most common.

Over the last few decades, genetic research has opened doors to improve the treatment of immune-mediated conditions like psoriasis, but there are still questions about how these diseases are triggered at the cellular level.

Researchers investigated the link between oxidative damage and DNA changes in people with psoriasis in a Brazilian study published in October 2022 in Anais Brasileiros de Dermatologia. Specifically, the research team investigated changes in oxidation telomere length, and DNA methylation status from the blood samples of 41 people with psoriasis.

Results from the study revealed increased levels of oxidative stress in DNA/RNA molecules in the serum samples of people with exacerbated psoriasis vulgaris compared to the healthy controls.

In particular, telomeres were longer—especially in females—but DNA methylation increases were not significant. Additionally, the study team pointed out that results were only minimally influenced by other demographic features like gender, a diagnosis of metabolic syndrome, and cigarette smoking.

The end result of this cellular damage, according to the report, appears to be the effect this cellular damage has on the proliferation of cells. Additionally, the report authors note that increased oxidation in serum samples correlated with the presence of chronic systemic inflammation—especially in patients who also had higher body weight, higher body-mass index, and/or metabolic syndrome.

Interestingly, previous research has indicated that increased telomere length typically corresponds with better health measures and an overall longer lifespan.

The study authors do question the lack of correspondence in their findings of longer telomere length alongside high levels of oxidative damage in the DNA of people with psoriasis. One theory is telomeres aren’t necessarily longer, but decrease in length at a slower speed, resulting in increased cell proliferation that leads to excess skin growth and other hyperactive immune responses in people with psoriasis.

Although the overall physiologic impact of longer telomere length in patients involved in the study was not quite clear, the authors say the data leaves a number of questions to be answered by future research, including how these genetic changes might be mitigated as a treatment strategy.

Oxidation is a well-documented contributor to accelerated cellular aging, the study notes, and elevated oxidative damage in other disease processes can be at least somewhat managed with antioxidant therapy.

Future research efforts, the authors suggest, could focus on better understanding how these genetic changes translate to clinical signs in different areas of the skin, as well as how specific genes could influence the pathogenesis of psoriasis vulgaris.

Reference

1. Beranek M, et al. Telomere length, oxidative stress and epigenetic changes in blood DNA of patients with exacerbated psoriasis vulgaris. Anais Brasileiros de Dermatologia. October 2022. Doi:10.1016/j.abd.2022.01.008