Association study between vitiligo and autoimmune‐related genes CYP27B1, REL, TNFAIP3, IL2 and IL21

Abstract

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

Transcriptome and Differential Methylation Integration Analysis Identified Important Differential Methylation Annotation Genes and Functional Epigenetic Modules Related to Vitiligo

“…Vitiligo is considered to be an autoimmune disease because cytokines such as (IFN)-γ, IL-1, IL-6, IL-8, and IL-10 are overexpressed in lesions, and activated CD8 + T lymphocytes, TH17, and other immune cells are significantly aggregated in the lesion area (16)(17)(18)(19). However, some researchers have suggested that autoimmunity may be secondary to high oxidative stress in vitiligo skin, leading to inherent defects of melanocytes and changes in its microenvironment (4).…”

Identification of active compounds in Vernonia anthelmintica (L.) willd by targeted metabolome MRM and kaempferol promotes HaCaT cell proliferation and reduces oxidative stress

“…VEGFA, also known as vascular endothelial growth factor A, is considered to be a particularly interesting candidate gene, which has been attributed to its polymorphisms, its correlation with autoimmune disorders, and its induction of angiogenic factor expression in vitiligo; moreover, VEGFA may be a potential target for late-onset vitiligo therapy ( Almasi-Nasrabadi et al, 2019 ). IL2 has been implicated in the regulatory pathways of autoimmune diseases, including signaling and promotion of the growth and proliferation of T cells; therefore, this protein plays an important role in generating immune responses ( Martins et al, 2020 ). Finally, MPO-specific markers are strongly associated with microscopic polyangiitis and other autoimmune diseases ( Prendecki et al, 2021 ).…”

Prevalence and burden of vitiligo in Africa, the Middle East and Latin America

“…40 Links between other gene candidates and vitiligo are under investigation. [42][43][44][45][46][47][48][49][50] 3.4 | Comorbidities, psychosocial effects and QoL…”

“…In addition, elevated serum TNFα levels have been associated with vitiligo in Iraqi 41 and Iranian patients 40 . Links between other gene candidates and vitiligo are under investigation 42–50 …”

“…40 Links between other gene candidates and vitiligo are under investigation. 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50…”