RESUMO
The aim of the present study was to explore whether the genes encoding interleukin (IL) 19, IL-20, IL-24 and 2 chains of the IL-20 receptor type I (IL-20-RI), IL-20RA and IL-20RB, located on chromosomes 1q32, 6q2223 and 3q22, respectively, are associated with vitiligo. The study involved 76 patients with vitiligo and 236 unrelated healthy volunteers. Genomic DNA was extracted from the whole blood and the frequencies of 20 single nucleotide polymorphisms were analysed by tetraprimer amplification refractory mutation system polymerase chain reaction. The minor allele of IL19 rs2243188 was significantly increased in vitiligo patients compared to controls (53.3 vs. 28.6%, adjusted p < 0.0001). The haplotype analysis revealed associations of 2 IL19/IL20 extended haplotypes (AACGTAA and ACCGTAA) and 2 IL20RB haplotypes (AGTA and AGGA) with vitiligo, remaining significant after correction for multiple testing. The A-to-C exchange at position IL19 rs2243188 leads to the loss of a nuclear receptor subfamily 2 factor binding site that is thought to influence mouse hippocampal development and neuronal differentiation. The third position of the IL20RB haplotypes is taken by rs747842 that induces the loss of the interferon regulatory factor 4 binding site that has an important role in the regulation of innate and adaptive immunity and in the signalling of pigmentation as well. In conclusion, the present study describes first-time associations between polymorphisms of genes of the IL19 cluster and their receptors and vitiligo, indicative of the part of IL19 and its receptor gene IL20RB in disease pathogenesis.
Assuntos
Interleucinas/genética , Receptores de Interleucina/genética , Vitiligo/genética , Adolescente , Adulto , Idoso , Alelos , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 3 , Cromossomos Humanos Par 6 , Feminino , Frequência do Gene , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto JovemAssuntos
Proteínas de Transporte/genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Adulto , Autofagia/genética , Proteínas Relacionadas à Autofagia , Intervalos de Confiança , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Transdução de Sinais/genética , Adulto JovemRESUMO
The expression pattern of several genes associated with different processes in melanocytes, including melanogenesis, is changed in vitiligo patients. We evaluated possible changes in the expression of interleukin (IL)-10 family cytokines (IL26, IL-28A, IL28B, IL29), their receptor subunits (IL20RB, IL22RA2, IL28RA), and genes potentially related to functioning of melanocytes (MDM1, IFNA1, IFNB1, IFNG, and ICAM1) in the case of vitiligo. We observed mRNA expression in vitiligo patients' and controls' skin and peripheral blood mononuclear cells using quantitative real-time polymerase chain reaction. The mRNA expression pattern of IL20RB, IL22RA2, IL-28A, IL28B, IL28RA, MDM1, IFNA1, IFNB1, IFNG, and ICAM1 changed in vitiligo skin and/or peripheral blood mononuclear cells (PBMC) compared with controls. All of these genes may potentially be involved in vitiligo pathogenesis through controlling or participating in different pathways that regulate survival/apoptosis, development and migration of melanocytes, and melanogenesis. This study presents additional support for our previous findings about the importance of IL-10 family cytokines in vitiligo, in particular the possible involvement of IL-22. Further studies should be considered.