Is vitiligo a hereditary disease?

Explained by a selective loss of melanocytes, the cells that synthesise melanin, the pigment that gives skin its colour, the vitiligo manifests visually through the appearance of white patches on the skin. While the body areas affected by vitiligo no longer have melanin, the melanoblasts, precursors of melanocytes located deeper in the skin, are still present. Their activation by certain vitiligo treatments allows for skin repigmentation. For a long time, vitiligo was considered a psychosomatic pathology. However, it is now known that it is largely based on a autoimmune mechanism , with a multifactorial origin.

Although vitiligo is not strictly speaking a hereditary disease, there are familial predispositions to developing it.

Extensive research has been conducted to elucidate the genetic factors contributing to the onset of vitiligo. Over 50 susceptibility genes have been associated with the disease, such as HLA, CTLA4, NLRP1, and TYR. Individuals carrying one or more variants of these genes are at a higher risk of developing the disease, but they will not necessarily be affected. The majority of loci, that is, the positions of genes on the chromosomes, associated with vitiligo code for genes involved in immune regulation, apoptosis, and melanocyte biology.

It is intriguing to note that the genes involved in the onset of vitiligo are not the same in all parts of the world. Thus, some are more commonly found in European populations, while others are more prevalent in China, Japan or India. A few examples of these peculiarities are presented in the table below.

For a number of these genes, causal genetic variants have been discovered, providing significant insight into the biological mechanisms underlying the risk of vitiligo attributable to these genes. Furthermore, together, the corresponding proteins define a functional network suggesting a general pathobiological pathway of damage to melanocytes, activation of immune cells, and targeting and apoptosis of melanocytes.

The genetic component of vitiligo has been particularly highlighted during genome-wide association studies, or GWAS in English. These studies rely on the analysis of specific genetic variations in the genome to identify those most often linked to a disease. Genome-wide association studies are based on the comparison of DNA from two large groups: a group composed of patients, referred to as the examined group, and a group composed of healthy subjects, or control group. They have been particularly useful in identifying the different susceptibility alleles for vitiligo.

• NATH S. & al. Genetic epidemiology of vitiligo: multilocus recessivity cross-validated. American journal of human genetics (1994).

• CZAJKOWSKI R. & al. Current aspects of vitiligo genetics. Advances in Dermatology and Allergology (2014).

• EZZEDINE K. & al. Vitiligo: A Review. Dermatology (2020).

• SPRITZ R. & al. The Genetic Basis of Vitiligo. Journal of Investigative Dermatology (2021).