Experimental Dermatology. 2020;29:535-538. | 535 wileyonlinelibrary.com/journal/exd 1 | BACKG ROU N D Vitiligo is a pigmentary disease characterized by epidermal melanocyte loss resulting in white patches on the affected skin areas.Autoimmunity has been well accepted as a possible cause for vitiligo; in addition, evidence of a polygenic transmission of common, low-effect-size risk alleles was found within multiplex-vitiligo-affected families, as well as high heritability (h 2 ~ 0.75), [1] suggesting an important genetic basis controlling susceptibility to the disease. Recently, genome-wide association studies (GWAS) have identified 50 loci, with each locus contributing a small amount to the overall vitiligo heritability. [1] Several of these genes encode for molecules involved in regulation of immune response, such as MHC genes, PTPN22, LPP, IL2RA and UBASH3A. Besides, candidate gene studies have identified association signals often concentrated among individuals or nuclear families presenting autoimmune comorbidities. [2,3] These findings suggest the existence of a shared genetic mechanism between vitiligo and other autoimmune disorders.
| QUE S TIONS ADDRE SS EDHere, we investigated genes previously related to autoimmune diseases for association with vitiligo, using two independent population samples of different designs.
AbstractThe aetiology of vitiligo has not been fully elucidated, and several hypotheses have been investigated; among them, the most explored assumes an autoimmune basis for the disease. Supporting this hypothesis is the frequent co-occurrence of autoimmune diseases with vitiligo. In addition, various genetic loci associated with vitiligo harbour key immune response genes. Our general hypothesis is that autoimmunity-associated genes participate in the control of vitiligo susceptibility. To investigate this hypothesis, we tested for association between vitiligo and genes CYP27B1, REL, TNFAIP3 and IL2/IL21, all previously related to autoimmune diseases associated with vitiligo. The study was performed using two independent population samples: a family-based discovery set (211 trios) and a replication set (131 cases/119 controls). Statistically significant association with vitiligo was detected between markers of the REL and IL2 gene in the family-based sample. Both association signals were concentrated among patients displaying autoimmune comorbidity and non-segmental vitiligo. Evidence for validation was detected for IL2 marker. Our findings suggest REL and IL2 as new vitiligo susceptibility genes and reinforce the hypothesis of a shared genetic mechanism controlling vitiligo and other autoimmune diseases.
K E Y W O R D Sautoimmunity, genetics, IL2, REL, vitiligo
