Risk Factor For Vitiligo Research Articles

Risk of vitiligo in patients with SARS-CoV-2 vaccination or infection: a nationwide cohort study.

As recent sporadic case reports of newly developed vitiligo after SARS-CoV-2 infection or vaccination have been -published, a convincing large-scale study addressing this association is warranted. To investigate the association between SARS-CoV-2 infection or vaccination and vitiligo using the Korean National Health Insurance Service database. SARS-CoV-2-positive patients and those vaccinated against SARS-CoV-2 were recruited. In studies 1 and 2, control groups were selected based on 1:1 propensity score matching with vaccinated and SARS-CoV-2-positive patients, respectively. The occurrence of vitiligo was the main outcome. Each individual was monitored for six months. The hazard ratio (HR) for vitiligo was calculated using the Cox proportional hazards model. In study 1, the incidence of vitiligo in the vaccination group was 2.22-fold higher than that in the non-vaccination group (adjusted HR [aHR]: 2.22; 95% confidence interval [CI]: 1.54-3.19). Rheumatoid arthritis was a risk factor for vitiligo (aHR: 1.99; 95%CI: 1.12-3.54). Conversely, two factors associated with decreased incidence of vitiligo were male sex (aHR: 0.58; 95%CI: 0.40-0.82) and rural residency (aHR: 0.68; 95%CI: 0.49-0.96). In study 2, the incidence of newly-diagnosed vitiligo was not significantly different between SARS-CoV-2-positive patients and uninfected controls (aHR: 0.95; 95%CI: 0.51-1.78). SARS-CoV-2 vaccination may increase the risk of developing vitiligo in South Korea, although additional studies in other countries or with extended periods are needed. Clinicians should be aware of the impact of SARS-CoV-2 infection and vaccination on autoimmune skin diseases, including vitiligo.

A comprehensive meta-analysis and prioritization study to identify vitiligo associated coding and non-coding SNV candidates using web-based bioinformatics tools

Vitiligo is a prevalent depigmentation disorder affecting around 1% of the general population. So far, various Genome Wide Association Studies (GWAS) and Candidate Gene Association Studies (CGAS) have identified several single nucleotide variants (SNVs) as a risk factor for vitiligo. Nonetheless, little has been discerned regarding their direct functional significance to the disease pathogenesis. In this study, we did extensive data mining and downstream analysis using several experimentally validated datasets like GTEx Portal and web tools like rSNPBase, RegulomeDB, HaploReg and STRING to prioritize 13 SNVs from a set of 291SNVs that have been previously reported to be associated with vitiligo. We also prioritized their underlying/target genes and tried annotating their functional contribution to vitiligo pathogenesis. Our analysis revealed genes like FGFR10P, SUOX, CDK5RAP1 and RERE that have never been implicated in vitiligo previously to have strong potentials to contribute to the disease pathogenesis. The study is the first of its kind to prioritize and functionally annotate vitiligo-associated GWAS and CGAS SNVs and their underlying/target genes, based on functional data available in the public domain database.

Relationship between risk factor and clinical type of vitiligo in dermatology and venerology outpatient clinic Dr. Soetomo General Academic Hospital Surabaya

Vitiligo is a skin and mucosa depigmentation condition caused by the loss of functioning melanocytes. Various pathological mechanisms are involved in melanocytes, their full details are often difficult to explain and several risk factors for vitiligo are thought to play a role. This study describe the relationship between risk factors and clinical type of vitiligo. This study is an analytic observational study with a retrospective cross sectional design based on the medical records patients who were treated in Dermatology and Venerology Outpatient Clinic Dr. Soetomo General Academic Hospital Surabaya. The result of this study found 115 new vitiligo patients with the following characteristics were female (53.9%), late adolescence (26.96%) and students (25.22%). The most common risk factors were idiopathic (51.3%) and emotional (28.7%). The most common clinical type was non-segmental vitiligo (53.04%). There was relationship between emotional and the clinical type of vitiligo (p=0.023 p<0.05) and there was relationship between idiopathic risk factors and the clinical type of vitiligo (p=0.019 p<0.05). There was relationship between emotional risk and idiopathic factors with the clinical type of vitiligo that were related to pathogenesis becomes important to understand to identify therapeutic targets and prognostic implications to stop the progression of the disease.

ASSOCIATION BETWEEN GENETIC VARIANTS OF SINGLE NUCLEOTIDE POLYMORPHISMS OF THE DISCOIDIN DOMAIN RECEPTOR TYROSINE KINASE 1 (DDR1) A/C (RS 2267641) AND GRANZYME B (GZMB) C/T (RS8192917) GENES IN VITILIGO

Vitiligo manifests as advanced loss of melanocytes with reduced cellular adhesion. Discoidin Domain Receptor Tyrosine kinase1 (DDR1) is a main element affecting cellular adhesiveness associated with vitiligo. Granzyme B (GZMB) has significant role in cytotoxic T-cell induced apoptosis. This study aimed to evaluate the association between genetic variants of single nucleotide polymorphisms of DDR1 A/C (rs 2267641) and GZMB C/T (rs8192917) and the risk of developing vitiligo. The genotypes were investigated using allele discrimination assay comparing 120 patients having non-segmental vitiligo and 100 age and gender matched healthy individuals. We detected a significant prevalence of the CC genotype and C allele of both DDR1 and GZMB polymorphisms in vitiligo patients with early onset and progressive course compared to controls. Our results concluded that DDR1 A/C (rs 2267641) and GZMB C/T (rs8192917) polymorphisms may be risk factors for vitiligo.

Homocysteine induces melanocytes apoptosis via PERK-eIF2α-CHOP pathway in vitiligo.

Vitiligo is a depigmentation disorder that develops as a result of the progressive disappearance of epidermal melanocytes. The elevated level of amino acid metabolite homocysteine (Hcy) has been identified as circulating marker of oxidative stress and known as a risk factor for vitiligo. However, the mechanism underlying Hcy-regulated melanocytic destruction is currently unknown. The present study aims to elucidate the effect of Hcy on melanocytic destruction and its involvement in the pathogenesis of vitiligo. Our results showed that Hcy level was significantly elevated in the serum of progressive vitiligo patients. Notably, Hcy induced cell apoptosis in melanocytes via activating reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-C/EBP homologous protein (CHOP) pathway. More importantly, folic acid, functioning in the transformation of Hcy, could lower the intracellular Hcy level and further reverse the apoptotic effect of Hcy on melanocytes. Additionally, Hcy disrupted melanogenesis whereas folic acid supplementation could reverse the melanogenesis defect induced by Hcy in melanocytes. Taken together, Hcy is highly increased in vitiligo patients at progressive stage, and our in vitro studies revealed that folic acid could protect melanocytes from Hcy-induced apoptosis and melanin synthesis inhibition, indicating folic acid as a potential benefit agent for patients with progressive vitiligo.

PM2.5 induces apoptosis, oxidative stress injury and melanin metabolic disorder in human melanocytes.

Recent growing evidence suggested that particulate matter 2.5 (PM2.5) has strong toxic effects on skin systems. However, the possible effects and the mechanisms of PM2.5 on vitiligo remain poorly understood. Therefore, the present study aimed to further investigate the effects and possible mechanisms of PM2.5 on vitiligo. Human keratinocytes (HaCaT cells) and human melanocytes (PIG1 cells and PIG3V cells) were exposed to PM2.5 (0-200 µg/ml) for 24 h. The cell viability of the three cell lines was measured by a Cell Counting Kit-8 assay. The secretions of stem cell factor (SCF) and basic fibroblast growth factor (bFGF) in HaCaT cells were evaluated by ELISA. The melanin contents, cellular tyrosinase activity, apoptosis, cell migration, malondialdehyde (MDA) contents, superoxide dismutase (SOD) levels, glutathione peroxidase (GSH-Px) levels and related protein expressions in PIG1 cells and PIG3V cells were evaluated by a NaOH assay, DOPA assay, Annexin V-FITC/Propidium Iodide staining, MDA assay, SOD assay, GSH-Px assay and western blotting, respectively. It was demonstrated that PM2.5 exposure inhibited cell viability of all three cell lines (HaCaT, PIG1 and PIG3V cells). PM2.5 exposure attenuated the secretions of SCF and bFGF in HaCaT cells. Moreover, PM2.5 exposure attenuated the activation of tyrosinase and melanogenesis, inhibited cell migration, and induced apoptosis and oxidative stress injury in PIG1 cells and PIG3V cells. In addition, PM2.5 exposure caused upregulated cytosolic cytochrome C and activated caspase-3 in PIG1 cells and PIG3V cells. Furthermore, PM2.5 exposure activated the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 signaling pathway. The present results suggested that PM2.5 exposure could inhibit the secretions of SCF and bFGF in keratinocytes, and cause oxidative stress injury and melanin metabolic disorder in melanocytes. Therefore, PM2.5 could be a new risk factor for vitiligo.

Is NAT2 Gene Polymorphism Associated with Vitiligo?

Background:N-acetyltransferase-2 (NAT2) is a phase II xenobiotic enzyme that plays an important role against oxidative stress-mediated reactive oxygen species protection. Polymorphism in specific genotypes of NAT2 may lead to increase an imbalance in antioxidant systems and may influence the pathogenesis of vitiligo. We conducted this study to see the association between NAT2 gene polymorphism and risk of vitiligo. We looked into whether single-nucleotide polymorphisms (SNP) at positions 857, 481 and 590 of the coding region of the NAT2 gene play as a risk factor for vitiligo among north Indian people.Methods:In this study, we assessed 100 patients with vitiligo and 160 healthy individuals as controls. Genomic DNA was extracted from human peripheral blood and polymerase chain reaction–restricted fragment length polymorphism was done to identify the single nucleotide polymorphism at positions 857, 481, and 590 of the coding region of the NAT2 gene.Results:In this study, we observed a significant higher risk with slow acetylator genotypes of NAT2 (OR = 2.85; 95% CI = 1.68-4.84, P value < 0.001) for the vitiligo. Furthermore, in the association between NAT2 acetylator genotypes with percentage of body surface area (BSA) of disease, we observed that slow acetylator genotypes of NAT2 has significant higher risk with low grade of disease (1%–10% >11%–30% >30% of BSA).Limitations:A major limitation of this study was the small sample size and warrants further investigation on a large epidemiological study to confirm these findings.Conclusions:Our preliminary data indicate that NAT2 slow acetylator genotype exhibits significant association for the risk of vitiligo, especially in disease predisposition and initiation.

An in-depth analysis identifies two new independent signals in 11q23.3 associated with vitiligo in the Chinese Han population

BackgroundVitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. ObjectiveThis study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population. MethodsWe selected and genotyped 26 SNPs at 11q23.3 in an independent cohort including 2924 cases and 4048 controls using the Sequenom MassArray iPLEX® system. Bonferroni adjustment was used for multiple comparisons and P value <1.92×10−3 (0.05/26) was considered statistically significant. ResultsThe A allele of rs613791 and G allele of rs523604 located in CXCR5 were observed to be significantly associated with vitiligo (OR=1.21, 95% CI: 1.11–1.31, P=1.20×10−5; OR=1.14, 95% CI: 1.07–1.23, P=1.90×10−4, respectively). The C allele of rs638893 (a previously reported one) located upstream of DDX6 was also significantly associated with vitiligo (OR=1.25, 95% CI: 1.12–1.38, P=3.04×10−5). The genotypes distribution of 3 SNPs also showed significant differences between case and control (rs613791: P=7.00×10−6, rs523604: P=4.00×10−3, rs638893: P=1.20×10−5, respectively). The two newly identified SNPs (rs613791 and rs523604) showed independent associations with vitiligo by linkage disequilibrium analysis and conditional logistic regression. ConclusionsThe study identified two new independent signals in the associated locus 11q23.3 for vitiligo. The presence of multiple independent variants emphasizes an important role of this region in disease susceptibility.

Association of Leukotrichia in Vitiligo and Asp148Glu Polymorphism of Apurinic/Apyrimidinic Endonuclease 1.

Background:Oxidative stress and increased DNA damage have been implicated in the etiopathogenesis of vitiligo. Oxidative DNA damage is mainly repaired by the base excision repair (BER) pathway.Aim:We sought to determine whether polymorphisms in DNA repair genes may have a role in the pathogenesis of vitiligo.Materials and Methods:We conducted a study including 100 patients with vitiligo and age- and sex-matched 193 control subjects to examine the role of single-nucleotide polymorphisms of BER genes, human 8-oxoG DNA N-glycosylase 1 (codon 326), apurinic/apyrimidinic endonuclease 1 (APE1) (codon 148), and X-ray repair cross-complementing group 1 (codon 399) as risk factors for vitiligo. These polymorphisms were determined by quantitative real-time polymerase chain reaction and melting curve analysis.Results:No significant association was observed between the variant alleles of studied genes and vitiligo.Conclusion:However, we showed that the presence of APE1 148Glu variant allele is associated with leukotrichia. This preliminary study suggests that APE1 (codon 148) polymorphism may play a role in vitiligo pathogenesis.

No Association between Vitiligo and Obesity: A Case-Control Study

Objective: The purpose of this study was to investigate the relationship between vitiligo and body mass index (BMI) to assess the possible association between vitiligo and obesity. Subjects and Methods: This was a case-control study on a total of 400 participants, i.e., 200 patients with vitiligo and 200 healthy volunteers. Medical assessments were performed by dermatologists using the modified Vitiligo European Task Force form. The height and weight of all of the participants were measured and used to calculate the BMI. Data were analyzed using multivariate logistic regression models. Adjustment for age and gender was carried out preliminarily in the case-control analysis, whereas a forward stepwise selection algorithm was used to assess which independent factors were associated with a BMI ≥30 or a BMI ≤18.5. Results: Comparison of the vitiligo and control groups revealed the absence of a significant association. The multivariate analysis of factors associated with a high BMI (≥30) in vitiligo patients showed a significant association between a high BMI and a sudden onset of vitiligo (p = 0.021; OR = 3.83; 95% CI 1.22-11.99) and the presence of inflammation and pruritus (p = 0.031; OR = 3.26; 95% CI 1.11-9.57). No significant association was observed in the analysis of factors associated with a low BMI (≤18.5) in vitiligo patients. Conclusion: In this study, vitiligo did not appear to be associated with a high BMI; obesity might not be a risk factor for vitiligo, in contrast to most autoimmune diseases which are significantly associated with obesity.

The Evaluation of Endothelin-1 and Endothelin Receptor Type A Gene Polymorphisms in Patients with Vitiligo.

Background:Endothelin-1 (EDN1) and EDN receptor type A (EDNRA) are implicated in melanocyte functions.Aim and Objectives:This study examines the role of EDN1 (G5665T and T-1370G) and EDNRA (C + 70G and G-231A) polymorphisms as a risk factor for vitiligo, and evaluates the relationship between genotypes and clinical characteristics of vitiligo patients.Materials and Methods:We analyzed genotype/allele distributions of EDN1 and EDNRA polymorphisms in 100 patients with vitiligo and 185 healthy controls by real-time polymerase chain reaction.Results:There was no notable risk for vitiligo afflicted by studied polymorphisms. However, the presence of EDNRA +70 variant G allele was found to be related with decreased risk for development of generalized type of vitiligo (odds ratio [OR]: 0.42, 95% confidence interval [CI] = 0.21–0.86, pcorr = 0.03) and showed protective effect against associated diseases seen in vitiligo (OR: 0.49, 95% CI = 0.27–0.88, pcorr = 0.034). Haplotype analysis demonstrated a strong (disequilibrium coefficient = 0.73, r2 = 0.405) linkage disequilibrium between EDN1 G5665T and T-1370G polymorphisms. The EDN1 5665/-1330 TT haplotype was over represented significantly in controls than in patients (P = 0.04).Conclusion:The studied polymorphisms do not seem to be a major risk for vitiligo. Haplotype analysis denoting protective effects against vitiligo may indicate an indirect interaction in the course of vitiligo. In addition, EDNRA + 70 polymorphism is protective against generalized type of vitiligo and associated diseases.

Association of FAS Gene Promoter Functional Polymorphisms and the Risk of Vitiligo in Turkish Populations

Background: The FAS/FASLG system shows a key role in regulating apoptosis. Objectives: Previous findings have indicated that a significantly increased risk of vitiligo was associated with FAS-1377 AA genotype and the FAS-1377 AG genotype when compared with FAS1377 GG genotype in Chinese population. Material and Methods: We investigated the FAS-670, FAS-1377, FAS-844 and FAS-124 polymorphisms in 113 vitiligo patients and also compared 196 controls. Results: We found that a significantly increased vitiligo was associated with the FAS-670 GA genotype [adjusted odds ratio (OR), 2.87; 95% confidence interval (CI), 1.37-6.03] when compared with the controls. However, there were no evident risk associated with FAS-1377, 844 and 124 genotypes. Conclusion: This is the first report of an association between FAS-670, FAS-1377, FAS-844 and FAS124 gene polymorphism and vitiligo in a Turkish population. The results of this study suggest that the presence of FAS-670 GA genotype can be regarded as risk factor for vitiligo, and especially for vitiligo in Turkish population.

Glutathione S-transferase M1 and T1 genetic polymorphism in Egyptian patients with nonsegmental vitiligo

Oxidative stress and accumulation of free radicals might play a role in the pathogenesis of vitiligo. Glutathione S-transferase (GST) is a multigene family of enzymes that detoxify oxidative stress products. In this study, genotyping by multiplex PCR of GSTM1 and GSTT1 in 101 women with nonsegmental vitiligo vulgaris and 101 age-matched healthy female volunteers showed that only the GSTM1 null genotype (P=0.04) was significantly overexpressed in patients with vitiligo. Analysis of the combined effect of GSTM1 and GSTT1 genotyping identified a significant association of risk for vitiligo with the GSTT1/GSTM1 double-null type only (P=0.01; OR=2.69; 95% CI 1.12-6.46). Age of onset of vitiligo was significantly earlier in patients with the T1 null genotype (P<0.01) and those with the T1-/M1+ and T1-/M1- combined genotypes (P<0.01 and P=0.01, respectively). In conclusion, the GSTM1 gene and the GSTM1/GSTT1 double-null genotype may be a risk factor for vitiligo in Egyptian patients. Inability to cope with oxidative stresses because of GST deficiency may cause early disease onset.

Association of halo nevus/i and vitiligo in childhood: a retrospective observational study

Although halo nevus (HN) is frequently observed, the relationship between vitiligo and HN in children has rarely been investigated. To investigate the association between HN and vitiligo in children and understand if HN/HNi might be a risk factor for vitiligo. Ninety-eight patients with only HN/HNi and 27 with HN/HNi and vitiligo were investigated for number and localization of HN/HNi, family history for HN/HNi and vitiligo and personal and family history for autoimmune or other diseases. A follow-up telephone interview was performed to investigate the evolution of HN/HNi and the possible onset of vitiligo and/or other diseases. In the HN/HNi and vitiligo group, HN/HNi and vitiligo had started almost simultaneously in 11 children; in nine, the onset of HN/HNi was followed by vitiligo after 6 months to 5 years; seven patients presented vitiligo first and HN/HNi after 3-9 years. Patients with associated vitiligo had, significantly more often, multiple HNi and a positive personal and/or family history of autoimmune thyroiditis compared with those with only HN/HNi. Follow-up longer than 5 years was available in 54/98 patients with only HN/HNi; two of them, both with multiple HNi, developed vitiligo. After follow-up, multiple HNi were noticed in 18/52 patients without vitiligo and in 9/11 of those in whom HN/HNi heralded vitiligo (s.s.). In patients with multiple HNi, the risk of vitiligo and other autoimmune diseases seems to be higher than in pediatric patients with a single HN; clinicians should pay particular attention to children with multiple HNi and personal or family history of autoimmune diseases.

Association of single nucleotide polymorphisms of Nrf2 promoter region with susceptibility to vitiligo

To investigate the association of the single nucleotide polymorphisms (SNPs) in Nrf2 promoter region with the susceptibility to risk of vitiligo. Samples of peripheral blood were collected from 300 vitiligo patients and 300 healthy persons. The genotypes of -686A/G, -684G/A, and -650C/A were detected by direct-sequencing. Genotyping of variable number of tandem repeat (VNTR) was performed by gene scan analysis with an ABI 310 Sequencer. Genetic and allelic frequencies were analyzed by Chi-square test and the risk was evaluated by calculating OR and 95% CI. There was statistical significant difference in genotypic and allelic frequencies of -650C/A between the vitiligo group and healthy control group (P < 0.05), and A -650 allele was associated with risk for vitiligo statistically significantly (OR = 1.724, 95% CI: 1.345-2.211, chi2 = 18.096, P < 0.01). Homozygote of A allele increased the risk for vitiligo obviously (OR = 2.902, 95% CI: 1.624-5.188, P < 0.01). No significant difference was found in other three polymorphisms between the two groups. polymorphism of Nrf2 promoter region -650C/A was associated with the development of vitiligo and A -650 allele may be one of risk factors for vitiligo.