Maire Karelson

Quality of life and emotional state in vitiligo in an Estonian sample: comparison with psoriasis and healthy controls.

The impact of vitiligo on quality of life is controversial. The aim of this study was to observe the impairment of quality of life and emotional state in adults with vitiligo compared with subjects with psoriasis and unaffected controls. The study group comprised 54 subjects with vitiligo, 57 with psoriasis and 57 unaffected controls. All subjects were examined and interviewed using the Dermatology Life Quality Index (DLQI) and Emotional State questionnaires. The total mean DLQI score in vitiligo was 4.7, compared with 0.6 in healthy controls (p<0.001) and 13.1 in psoriasis (p<0.001). In vitiligo, females experienced a greater impact on feelings and men experienced a greater impact on relationships. Lower quality of life in vitiligo was associated with active stage of the disease, extension of pigment loss, depigmentation on the hands, and earlier onset of disease. The results demonstrate that vitiligo has less impact on quality of life than psoriasis.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.

Gene expression study of IL10 family genes in vitiligo skin biopsies, peripheral blood mononuclear cells and sera

Background  Vitiligo is a pigmentation disorder, the cause of which is complex and not yet fully understood. There is a significant change of epidermal cytokines in involved skin of patients with vitiligo compared with uninvolved skin and skin of healthy controls, thus suggesting a possible involvement of cytokines in the pathogenesis of vitiligo.

Expressional changes in the intracellular melanogenesis pathways and their possible role the pathogenesis of vitiligo

BACKGROUND Main pathway in human melanocytes through which signal from the melanocortin system reaches the melanogenesis enzymes is cAMP/PKA pathway and it is modulated by Wnt and MAPK pathways. In our previous study we established significant increase of melanocortin receptor expression in unaffected skin of vitiligo patients compared to healthy subjects. OBJECTIVE The aim of this study was to assess the gene expression profile of the intracellular signalling pathways linking melanocortin system with enzymes involved in melanogenesis. METHODS Using QRT-PCR method, mRNA expression levels of eight genes related to signal transduction from the melanocortin system to melanogenesis enzymes was measured in lesional and non-lesional skin of vitiligo patients and in the skin of healthy control subjects. Following genes were analyzed in the study: MITF, CREB1, p38, USF1, PIK3CB (PI3K), RPS6KB1, LEF1 and BCL2. RESULTS The mRNA levels of MITF, LEF1, p38, PIK3CB and RPS6KB1 were decreased in lesional skin of vitiligo patients compared to skin of healthy control subjects. We also found increased expression of USF1 and BCL2 in non-lesional skin of vitiligo patients compared to skin of healthy control subjects. mRNA levels of MITF and BCL2 were decreased in lesional skin of vitiligo patients compared to non-lesional skin of vitiligo patients. CONCLUSIONS Present study indicates increased expression of the genes of the intracellular melanogenesis pathway in the non-lesional skin of vitiligo patients. This finding suggests activation of melanogenesis pathway in the non-lesional skin of vitiligo.

Terbinafine: efficacy and tolerability in young children with tinea capitis due to Microsporum canis

Aims  We carried out an open, prospective, uncontrolled study to evaluate the efficacy and tolerability of terbinafine in the treatment of young children with tinea capitis due to Microsporum canis.

Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

BackgroundMYG1 (Melanocyte proliferating gene 1, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that MYG1 mRNA expression is elevated in the skin of vitiligo patients. Our aim was to examine nine known polymorphisms in the MYG1 gene, to investigate their functionality, and to study their association with vitiligo susceptibility.MethodsNine single nucleotide polymorphisms (SNPs) in the MYG1 locus were investigated by SNPlex assay and/or sequencing in vitiligo patients (n = 124) and controls (n = 325). MYG1 expression in skin biopsies was detected by quantitative-real time PCR (Q-RT-PCR) and polymorphisms were further analysed using luciferase and YFP reporters in the cell culture.ResultsControl subjects with -119G promoter allele (rs1465073) exhibited significantly higher MYG1 mRNA levels than controls with -119C allele (P = 0.01). Higher activity of -119G promoter was confirmed by luciferase assay. Single marker association analysis showed that the -119G allele was more frequent in vitiligo patients (47.1%) compared to controls (39.3%, P < 0.05, OR 1.37, 95%CI 1.02-1.85). Analysis based on the stage of progression of the vitiligo revealed that the increased frequency of -119G allele occurred prevalently in the group of patients with active vitiligo (n = 86) compared to the control group (48.2% versus 39.3%, P < 0.05; OR 1.44, 95%CI 1.02-2.03). Additionally, we showed that glutamine in the fourth position (in Arg4Gln polymorphism) completely eliminated mitochondrial entrance of YFP-tagged Myg1 protein in cell culture. The analysis of available EST, cDNA and genomic DNA sequences revealed that Myg1 4Gln allele is remarkably present in human populations but is never detected in homozygous state according to the HapMap database.ConclusionsOur study demonstrated that both MYG1 promoter polymorphism -119C/G and Arg4Gln polymorphism in the mitochondrial signal of Myg1 have a functional impact on the regulation of the MYG1 gene and promoter polymorphism (-119C/G) is related with suspectibility for actively progressing vitiligo.

Association analysis of genes of the IL19 cluster and their receptors in vitiligo patients.

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, 6q22–23 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.

Expression Profile of Genes Associated with the Dopamine Pathway in Vitiligo Skin Biopsies and Blood Sera

Background: Dopamine has been proven to be toxic for melanocytes. In vitiligo patients the level of dopamine is increased and the functioning of several enzymes participating in the dopamine pathway is changed. Methods: With the use of quantitative real-time polymerase chain reaction and ELISA the expression of genes connected to the dopamine pathway (PAH, PCD, TH, DDC, DBH, PNMT, GPX1, MAOA, MAOB, COMT, DRD1–DRD5, VMAT1 and VMAT2) was observed in vitiligo patients’ and control subjects’ skin and blood. Results: The mRNA expression of GPX1, DDC, MAOA, DRD1 and DRD5 differs in vitiligo skin and the protein level of DDC, MAOA, MAOB, DRD1 and DRD5 is changed in vitiligo patients’ skin and/or blood sera. Conclusions: The dopamine pathway probably influences melanogenesis directly or through the melanocortin pathway. We provide new data about changes of expression profile of the dopamine-synthesizing enzyme DDC, the dopamine-degrading enzymes MAOA and MAOB and the D1-like family dopamine receptors in vitiligo skin and blood sera.

Differences between familial and sporadic cases of vitiligo.

Background  Most cases of vitiligo are sporadic, but about 10–36% of the patients have positive family history.

Association analysis of class II cytokine and receptor genes in vitiligo patients.

The loss of melanocytes in vitiligo is mainly attributed to defective autoimmune mechanisms and lately autoinflammatory mediators have become more emphasized. Among these, a number of class II cytokines and their receptors have displayed altered expression patterns in vitiligo. Thus, we selected 30 SNPs from the regions of respective genes to be genotyped in Estonian case-control sample (109 and 328 individuals, respectively). For more precise analyses, patients were divided into subgroups based on vitiligo progression activity, age of onset, sex, occurrence of vitiligo among relatives, extent of depigmented areas, appearance of Köbners phenomenon, existence of halo nevi, occurrence of spontaneous repigmentation, and amount of thyroid peroxidase antibodies. No associations appeared in whole vitiligo group. In subgroups, several allelic and haplotype associations were found. The strongest involved SNPs rs12301088 (near IL26 gene), that was associated with familial vitiligo and existence of halo nevi, and rs2257167 (IFNAR1 gene), that was associated with female vitiligo. Additionally, haplotypes consisting of rs12301088 and rs12321603 alleles (IL26-IL22 genes), that were associated with familial vitiligo and existence of halo nevi. In conclusion, several genetic associations with vitiligo subphenotypes were revealed and functional explanations to these remain to be determined in respective studies.