A genetic link established in the case of rosacea?

Rosacea: Are there genetic predispositions to developing this dermatosis?

Rosacea is a skin condition that is widely prevalent in France and around the world. Over the past few decades, several hypotheses have been proposed regarding the causes of this disease, and various sources attribute rosacea to a hereditary origin. Discover below whether the scientific literature truly mentions genetic predispositions to developing rosacea.

Published on September 12, 2024, by Marie, Scientific Editor — 5 min of reading

Is rosacea a hereditary condition?

Rosacea is an inflammatory and chronic dermatosis, predominantly affecting the face, rosacea is characterised by a widespread and extensive redness, sometimes accompanied by a dilation of small blood vessels, making them visible. Other symptoms often accompany this disease, such as hot flushes, skin hypersensitivity or burning sensations. In some cases, rosacea can progress and lead to the appearance of spots, a significant thickening of the skin, or even affect the eyes.

While the causes of rosacea are still poorly understood and appear to be multifactorial, one hypothesis stands out in the scientific community: that of a genetic predisposition to develop this dermatosis. This suspicion comes notably from the frequency of rosacea occurrence in subjects with very fair skin and eyes. It has indeed been observed that people from Northern Europe, predominantly presenting phototypes I to III, are more affected by the disease than those with darker skin.

According to some epidemiological data, up to 30% of individuals with rosacea have a family history of this condition.

A study conducted by POPKIN in 2015 aimed to highlight the link between genetics and the development of rosacea. For this purpose, 233 pairs of monozygotic twins and 42 pairs of dizygotic twins, totalling 550 individuals, were surveyed to determine if they exhibited symptoms of rosacea. As a reminder, monozygotic twins share almost 100% of their genetic material, while dizygotic twins share about 50% of common genes. By observing the incidence of rosacea among the different twins, as well as their lifestyle habits, the researchers were able to establish a genetic correlation percentage, evaluated here at 46%. According to this study, rosacea appears to be attributable in equal parts to genetic factors and environmental factors, such as exposure to UV rays, alcohol consumption or smoking.

Rosacea and genetics: what are the mechanisms involved?

While it appears that rosacea may be partly due to genetic predispositions, the involved genes and underlying mechanisms are not yet fully understood. However, several genetic analyses have demonstrated the existence of a specific polymorphism, called rs763035, which would be associated with rosacea. This is located between the HLA-DRA and BTLN2 genes. As a reminder, polymorphism refers to the different forms a single gene can take. Based on these findings, it would seem that rosacea is linked to three class II HLA alleles, the same ones involved in the development of type I diabetes retinopathy. This hypothesis aligns with other epidemiological observations showing an association of rosacea with certain autoimmune diseases.

A study conducted by OUSSEDIK in 2018 also delved into the genetics of rosacea in an effort to better understand its mechanisms. The researchers particularly examined the anti-microbial peptides secreted by keratinocytes and their role in the genetic predispositions of rosacea. Fundamentally, these peptides are found in the sebaceous glands and serve as an endogenous defence against external microorganisms. In addition to their antimicrobial function, some of these peptides, such as linear cationic α-helical peptides like LL-37, a human cathelicidin, can also increase the production of cytokines, thereby contributing to inflammation. LL-37 is also suspected of playing a role in skin immunity and its dysfunction could influence the pathogenesis of rosacea.

Indeed, the analysis of transcription in a murine model has established that the cathelicidin LL-37 was upregulated in the case of rosacea. Researchers have also shown that the overexpression of LL-37 was linked to an increase in the transcription of TRPV4 in mast cells. Now, TRPV4 partly ensures skin homeostasis and the maintenance of the skin barrier. A disruption in the expression of this gene could therefore also be implicated in the development of rosacea.

Even though some mechanisms are beginning to become clear, progress in understanding the genetic component of rosacea remains necessary in order to develop targeted therapies and improve the management of the disease.