Roles of blood metabolites in mediating the relationship between vitiligo and autoimmune diseases: Evidence from a Mendelian randomization study.

OBJECTIVE: This study employed Mendelian Randomization (MR) to investigate the causal relationship between genetic susceptibility to vitiligo and the risk of various autoimmune diseases, along with the mediating role of blood metabolites. METHODS: We performed two-sample MR analyses using aggregated genome-wide association studies (GWAS) data on 486 blood metabolites, vitiligo, and nine autoimmune diseases to investigate blood metabolites' causal effects on the susceptibility of vitiligo and the associations of vitiligo with nine autoimmune comorbidities. We also applied multivariable MR to unravel metabolites by which vitiligo influences the pathogenesis of autoimmune diseases. RESULTS: Our findings indicate that vitiligo amplified the risk of several autoimmune diseases, including rheumatoid arthritis (OR 1.17; 95 % CI 1.08-1.27), psoriasis (OR 1.10; 95 % CI 1.04-1.17), type 1 diabetes (OR 1.41; 95 % CI 1.23-1.63), pernicious anemia (OR 1.23; 95 % CI 1.12-1.36), autoimmune hypothyroidism (OR 1.19; 95 % CI 1.11-1.26), alopecia areata (OR 1.22; 95 % CI 1.10-1.35), and autoimmune Addison's disease (OR 1.22; 95 % CI 1.12-1.33). Additionally, our analysis identified correlations with vitiligo for 14 known (nine risk, five protective) and seven uncharacterized serum metabolites. After adjusting for genetically predicted levels of histidine and pyruvate, the associations between vitiligo and these diseases were attenuated. CONCLUSIONS: We substantiated vitiligo's influence on susceptibility to seven autoimmune diseases and conducted a thorough investigation of serum metabolites correlated with vitiligo. Histidine and pyruvate are potential mediators of vitiligo associated with autoimmune diseases.By combining metabolomics with genomics, we provide new perspectives on the etiology of vitiligo and its immune comorbidities.

Assessment of serum granulysin and cathepsin-L levels in vitiligo patients.

OBJECTIVE: Cellular and humoral immunity plays a role in the pathogenesis of vitiligo. T lymphocytes and natural killer cells involved in cellular immunity carry out their cytotoxic activities through perforin/granzyme-dependent granule exocytosis, in which granulysin and cathepsin-L are also involved. The aim of this study was to investigate the possible role of serum granulysin and cathepsin-L in the etiopathogenesis of vitiligo and their association with disease activity and severity. METHODS: This randomized, prospective case-control study was conducted with 46 vitiligo patients admitted to the hospital for vitiligo between January and November 2021 and 46 healthy volunteers of similar age and gender. Serum levels of granulysin and cathepsin-L were measured by the enzyme-linked immunosorbent assay method. RESULTS: The mean serum levels of granulysin and cathepsin-L were statistically significantly higher in vitiligo patients compared with the control group (p=0.048 and p=0.024, respectively). There was no statistically significant correlation between serum granulysin and serum cathepsin-L levels and disease severity in the patient group (r=0.30, p=0.062 and r=0.268, p=0.071, respectively). Disease activity also showed no significant association with serum granulysin and cathepsin-L levels (p=0.986 and p=0.962, respectively). CONCLUSION: Although granulysin and cathepsin-L are molecules involved in the pathogenesis of vitiligo, the use of these molecules may not be helpful in assessing disease activity and severity. It may be helpful to conduct comprehensive and prospective studies to find new molecules to fill the gap in this area.

Expression patterns of long non-coding RNAs in peripheral blood mononuclear cells of non-segmental vitiligo.

OBJECTIVE: We explored the patterns of long non-coding RNA (lncRNA) expression in peripheral blood mononuclear cells (PBMCs) from patients with non-segmental vitiligo. METHODS: We used high-throughput RNA sequencing technology to generate sequence data from five patients with non-segmental vitiligo alongside five normal healthy individuals, and then performed bioinformatics analyses to detect the differential expression of lncRNA in PBMCs. Gene Ontology (GO) and pathway analyses were performed for functional annotation, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify gene expression. Target miRNAs and mRNAs of differentially expressed lncRNAs were predicted using bioinformatics analysis. RESULTS: A total of 292 lncRNAs were differentially expressed in non-segmental vitiligo (fold change ≥ 2.0, P < .05), of which 171 were upregulated and 121 were downregulated. Six differentially expressed lncRNAs were selected, namely ENST00000460164.1, ENST00000393264.2, NR-046211.1, NR-135491.1, NR-135320.1, and ENST00000381108.3, for validation by qRT-PCR. The results showed that ENST00000460164.1 and NR-046211.1 were highly expressed in PBMCs of non-segmental vitiligo. An lncRNA-miRNA-mRNA network containing two lncRNAs, 17 miRNAs, and 223 mRNAs was constructed. CONCLUSION: Our results revealed patterns of differentially expressed lncRNAs in the PBMCs of non-segmental vitiligo individuals. ENST00000460164.1, and NR-046211.1 may be potential biomarkers and drug targets for the treatment of non-segmental vitiligo.

Can monocyte to HDL cholesterol ratio and monocyte to lymphocyte ratio be markers for inflammation and oxidative stress in patients with vitiligo? A preliminary study.

Both systemic inflammation and oxidative stress play crucial roles in the pathogenesis of vitiligo. In recent studies, monocyte to high-density lipoprotein cholesterol ratio (MHR), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV) and plateletcrit (PCT) have been shown to reflect inflammation and oxidative stress in chronic inflammatory and autoimmune diseases. In this study, we aimed to investigate the hematological and inflammatory parameters in patients with vitiligo and to evaluate their possible relationship with disease severity. The parameters including MHR, MLR, NLR, PLR, MPV, and PCT were retrospectively investigated in patients with vitiligo and healthy controls. Disease severity was evaluated using the vitiligo extent tensity index (VETI) score. A total of 180 patients with vitiligo, and age-gender-matched 180 healthy controls were enrolled in the study. MHR, MLR, PLR, PCT values were found to be significantly higher in patients with vitiligo (p < 0.05). MPV and NLR values showed no statistically significant difference between the two groups. A positive correlation was also detected between MHR and MLR values, disease duration, and VETI score (p < 0.05). We suggest that MHR and MLR can be used as markers of inflammation and oxidative stress in patients with vitiligo. Both markers may also reflect disease severity.

Serum level of S100B in vitiligo patients: Is it a marker of disease activity?

BACKGROUND: Vitiligo is a chronic depigmentary skin disorder, characterised clinically by the development of white macules and or patches caused by loss of epidermal melanocytes. S100B is a dual function protein released from epidermal melanocytes in response to injury. It considered a possible marker of disease activity in both malignant melanoma and vitiligo. AIM OF THE STUDY: To estimate the serum level of S100B level in vitiligo patients and correlate its level with disease activity and various disease parameters. PATIENTS AND METHODS: Sixty vitiligo patients and 60 healthy volunteers as controls were included in the study. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity (VIDA) scores were estimated for each patient. Quantitative assessment of S100B level using ELISA technique was done for all participants. RESULTS: S100B level was significantly correlated with the presence of vitiligo (P = 0.01), while it showed no correlation with the disease activity using VASI or VIDA scores. As regards the receiver operating characteristic (ROC) curve analysis of S100B for diagnosis and discrimination of vitiligo, serum S100B showed area under the curve (AUC) of 0.781 with 73.3% sensitivity and 80% specificity. CONCLUSION: The serum level of S100B was related to the presence of vitiligo, but its level did not show any relation to the disease activity using either VASI and VIDA scores or various disease parameters.

LRP1/CD91 is highly expressed in monocytes from patients with vitiligo - even after repigmentation.

Vitiligo pathophysiology is mediated by antigen-specific cytotoxic T cells. Environmental stressors cause susceptible melanocytes to secrete damage-associated molecular patterns (DAMPs). DAMPs are recognized by receptors such as the endocytic low-density lipoprotein receptor-related protein (LRP1/CD91), expressed in antigen-presenting cells, which activate self-reactive CD8+ T cells, leading to melanocyte destruction. Within this response, interferon gamma triggers production of cytokine CXCL10, recruiting more activated T cells causing further melanocytic damage. We hypothesized that expression of LRP1/CD91 was higher in vitiligo patients compared to non-vitiligo individuals. And further that levels/expression of CXCL10 in plasma were linked to disease severity. We enrolled forty individuals in this study: 18 patients with vitiligo and 22 healthy volunteers. We assessed LRP1/CD91 expression and plasma CXCL10 in patients with vitiligo and healthy volunteers. Additionally, vitiligo patients received combined treatment for 16 weeks following which the said parameters were reassessed. Vitiligo Area Scoring Index was calculated before and after treatment for these patients. Analysis of LRP1/CD91 MFI values in monocytes from vitiligo patients showed high surface levels of LRP1/CD91 than from healthy volunteers (10.50 ± 0.77 vs. 6.55 ± 0.77 MFI units, p < 0.001). This expression did not change after treatment. Plasma levels of CXCL10 were higher in vitiligo patients than healthy volunteers (93.78 ± 7.73 vs. 40.17 ± 6.25 pg/ml). The patients with a good clinical response to treatment had a parallel reduction in plasma CXCL10 levels (105.8 ± 18.44 vs. 66.13 ± 4.87 pg/ml) before and after treatment. LRP1/CD91 expression may reflect susceptibility to vitiligo. Plasma levels of CXCL10 can represent a biomarker for monitoring treatment response. LRP1 and CXCL10 may represent therapeutic targets.

MicroRNA­21­5p protects melanocytes via targeting STAT3 and modulating Treg/Teff balance to alleviate vitiligo.

Vitiligo (VIT) is caused by loss and degradation of functional epidermal melanocytes. Studies have indicated that melanocyte destruction may be associated with an imbalance between regulatory T cells (Treg cells) and effector T cells (Teff cells). The current study aimed to investigate the molecular mechanism through which Treg/Teff balance affects VIT pathogenesis. To explore this, peripheral blood mononuclear cells were isolated from patients with VIT and healthy individuals. The present study revealed that the proportions of CD4+ T cells, Treg cells and T helper 1 (Th1) cells were decreased in patients with VIT, but those of Teff cells (Th17 and Th22 cells) were increased; additionally, Foxp3 expression was decreased, but the expression levels of interferon­Î³, interleukin (IL)­17A and IL­22 were increased. Furthermore, in patients with VIT, microRNA (miR)­21­5p expression was decreased, while that of STAT3 was increased. Further in vitro experiments in CD4+ T cells revealed that STAT3 was targeted by miR­21­5p. Functional analysis further indicated that miR­21­5p overexpression in Th17­polarized CD4+ T cells decreased the proportion of Teff cells and associated cytokines, such as IL­17A and IL­22, but increased the proportion of Treg cells and Foxp3. However, the effects of miR­21­5p overexpression were partly reversed by STAT3 overexpression. Increased apoptosis of melanocytes was detected after co­culture with Th17­polarized CD4+ T cells in the presence of a miR­21­5p mimic. However, this indirect effect of the miR­21­5p mimic on melanocytes was decreased via STAT3 overexpression. Therefore, miR­21­5p may protect melanocytes via targeting STAT3 and regulating Treg/Teff balance. The current findings may provide a possible treatment method for managing VIT.

Differentially expressed microRNAs in peripheral blood mononuclear cells of non-segmental vitiligo and their clinical significance.

BACKGROUND: Vitiligo is a frequent acquired depigmentation skin disease due to a loss of melanocytes. This study sought to characterize the expression pattern of microRNA (miRNA) in the peripheral blood mononuclear cells (PBMCs) of non-segmental vitiligo (NSV) patients. We also screened for molecular markers that can be used to evaluate the clinical stages of NSV. METHODS: The miRNA expression profile in the PBMCs of four patients with progressive NSV and four healthy controls was determined using high-throughput RNA sequencing. The divergently expressed miRNA was verified via qRT-PCR in 26 progression, 26 stable NSV, and 26 healthy controls. RESULTS: Our findings posited that 323 miRNAs were differentially expressed in the PBMCs of NSV patients. The top 10 up-regulated miRNAs in patients were hsa-miR-335-5p, hsa-miR-20a-5p, hsa-miR-514a-3p, hsa-miR-144-5p, hsa-miR-450b-5p, hsa-miR-369-3p, hsa-miR-101-3p, hsa-miR-142-5p, hsa-miR-19b-3p, and hsa-miR-340-5p. The top 10 down-regulated miRNAs in patients were hsa-miR-4443, hsa-miR-1248, hsa-miR-6859-3p, hsa-miR-668-3p, hsa-miR-7704, hsa-miR-323a-5p, hsa-miR-1237-3p, hsa-miR-3127-3p, hsa-miR-6735-3p, and hsa-miR-127-3p. The expressions of hsa-miR-20a-5p in PBMCs of progressive and stable NSV were remarkably elevated relative to the healthy controls. In the characteristics curve analysis of hsa-miR-20a-5p for differentiating progressive and stable NSV from normal subjects in PBMCs, the area under curve (AUC) was 0.92 and 0.81. Compared with patients in stable NSV, the hsa-miR-20a-5p was markedly increased in PBMCs of progressive NSV patients, and the AUC was 0.81. CONCLUSION: Our results showed that divergently expressed miRNAs contribute to the pathogenesis of NSV and that hsa-miR-20a-5p can be applied as a biosignature for stage assessment in PBMCs of patients with NSV.

Serum levels of miRNA-21-5p in vitiligo patients and effects of miRNA-21-5p on SOX5, beta-catenin, CDK2 and MITF protein expression in normal human melanocytes.

BACKGROUND: Epigenetics of vitiligo was evaluated in few studies. In particular, the role of miR-21, a microRNA involved in various processes, including melanogenesis, was never investigated. OBJECTIVE: Evaluation of serum levels of miR-21-5p in vitiligo patients and miR-21-5p effects on melanogenesis. METHODS: We measured serum levels of miR-21-5p in 40 patients affected by nonsegmental vitiligo and 40 sex- and age-matched healthy controls. Next, normal human melanocytes were transfected with miR-21-5p to study the effects of this microRNA, which targeted some proteins involved in melanogenesis pathway like SOX5, beta-catenin, cyclin-dependent kinase 2 (CDK2), and MITF. RESULTS: The expression of miR-21-5p in vitiligo patients was 3.6-4454.4 fold (mean 990.4 ± 1397.9) higher than in controls. The relative expression of miR-21-5p was directly and significantly correlated with disease severity, defined by VASI (Vitiligo Area and Severity Index) score (Rho = 0.89, p = 10-7), but not other individual or clinical characteristics. In the second part of the study, a significant reduction of SOX5, beta-catenin and CDK2 protein expression and increase of MITF protein expression was observed in cultured melanocytes after 24 h trasfection with miR-21-5p. CONCLUSION: According to literature, miR-21-5p upregulation and consequent SOX5 downregulation should upregulate melanogenesis, while vitiligo is characterized by skin depigmentation. Our results suggest that current knowledge of the pathogenesis of vitiligo is probably incomplete. Clinical manifestations could result from an altered balance between metabolic pathways with contrasting effects. In this view, miR-21-5p upregulation might be a tentative compensation mechanism. Further studies appear necessary to confirm and better understand our results and their importance.

Increased level of cathelicidin (LL-37) in vitiligo: Possible pathway independent from vitamin D receptor gene polymorphism.

Vitiligo is a multifactorial skin disease with established role of genetics and autoimmunity in its pathogenesis. Vitamin D receptor (VDR) polymorphisms have been suggested to correlate with risk of vitiligo in some ethnic populations. On the other hand, cathelicidin, one of the innate immune system components, has a role in development of some chronic skin diseases and VDR regulates the expression of cathelicidin. We aimed to determine the plasma level of cathelicidin and its association with the VDR gene polymorphisms as well as plasma vitamin D level in patients with vitiligo. Ninety vitiligo patients and 90 non-vitiligo controls participated in this study. Blood levels of 25(OH) vitamin D and cathelicidin were determined with ELISA. Genotyping for VDR polymorphisms (ApaI, TaqI, FokI and BsmI) was done with RFLP-PCR method. Mean blood level of cathelicidin was significantly higher in vitiligo patients as compared to controls (P < .0001). Mean blood level of vitamin D was significantly lower in patients than controls (P = .01). Statistically significant differences were not observed for both genotype and allele frequencies of BsmI, ApaI and TaqI polymorphisms. There was a borderline increased risk of vitiligo in over-dominant model of FokI polymorphism with OR = 1.8 and P = .051. Our findings was suggestive of the potential role of cathelicidin in the pathogenesis of vitiligo; however, future evaluations are needed to determine its precise mechanism. Genetic study of VDR gene polymorphism was suggestive of increased risk of vitiligo in association with a FokI polymorphism in Iranian population.

Selenium Level in Patients with Vitiligo: A Meta-Analysis.

BACKGROUND: It has been reported that deficiency of selenium can cause autoimmune disease. This meta-analysis was aimed at evaluating whether there exits an association between selenium level and vitiligo. METHODS: A comprehensive search was conducted on PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Med Online, and China VIP databases from the inception to February 12, 2019. The main outcome was the standardized mean difference (SMD) with 95% confidence interval (CI) in serum selenium level between vitiligo patients and healthy controls. RESULTS: A total of 8 studies with 305 vitiligo patients and 6156 healthy controls were included in this meta-analysis. The results showed that there was no significant difference in selenium level between vitiligo patients and healthy controls (SMD = 0.481, 95%CI = -0.642 to 1.604, Z = 0.840, P > 0.05). Further subgroup analysis stratified by area revealed that Asian vitiligo patients had decreased selenium level, while that finding was not observed in Caucasian patients (Asian: SMD = -0.303, 95%CI = -0.603 to -0.004, P < 0.05; Caucasian: SMD = 0.957, 95%CI = -0.752 to 2.665, P > 0.05). CONCLUSIONS: Although overall selenium level was similar between vitiligo patients and health controls, subgroup analysis showed decreased levels of selenium in Asian vitiligo patients. It may suggest a clinical tailored administration of selenium supplementation in Asian vitiligo patients.

Macrophage inhibitory factor (MIF) gene polymorphisms are associated with disease susceptibility and with circulating MIF levels in active non-segmental vitiligo in patients from western Mexico.

BACKGROUND: The macrophage migration inhibiting factor (MIF) is a protein that promotes the activation of immune cells and the production of other proinflammatory cytokines such as TNF-α, IL-1ß, and IFN-γ, which have proposed to play an essential role in the pathogenesis of vitiligo. The study aimed to assess the association between MIF polymorphisms (-794 CATT5-8 and -173 G>C), MIF in situ expression, and MIF serum concentrations with susceptibility and disease activity in patients with non-segmental vitiligo (NSV) from western Mexico. METHODS: The study included 111 patients with NSV and 201 control subjects. Genotyping was performed by conventional PCR (-794 CATT5-8 ) and PCR-RFLP (-173 G>C) methods. MIF mRNA expression was quantified by real-time PCR and MIF serum concentrations were determined by ELISA kit. Histopathological samples were analyzed by automated immunohistochemistry. RESULTS: The MIF polymorphisms were associated with NSV susceptibility. Serum concentrations of MIF were higher in patients with active NSV and correlated negatively with the years of evolution. The depigmented skin from patients with active vitiligo showed a high expression of MIF. CONCLUSION: MIF polymorphisms increase the risk of NSV in the western Mexican population. The serum concentrations of MIF and in situ expression are associated with active NSV.

Serum level of antioxidant vitamins and minerals in patients with vitiligo, a systematic review and meta-analysis.

BACKGROUND: Antioxidant status is considered as important factor in the pathogenesis of vitiligo. However, there are controversial findings about serum status of antioxidants in vitiligo patients. The purpose of this study was to systematically review the evidences comparing the serum levels of antioxidant vitamins and minerals between vitiligo patients and controls, and performing meta-analysis of the results. METHODS: A comprehensive search was performed for studies comparing the serum status of antioxidant vitamins and minerals using following databases since inception up to 30 April 2020; PubMed, EMBASE, Scopus, and Web of Science. Data extraction was done by two independent reviewers. The data was pooled for serum level of each antioxidant comparing between vitiligo and control groups. RESULTS: Thirteen studies were included in this systematic review. The serum level of vitamin A, C, E, selenium, zinc and copper were compared between vitiligo patients and controls in these studies. Eleven studies including 570 vitiligo cases and 580 controls were included in the meta-analysis. Serum vitamin A and copper level in vitiligo patients were only evaluated in single studies and not included in meta-analysis. Based on fixed effect model, there were no statistical difference between two groups regarding serum vitamin C (OR = 1.17, 95 % CI, 0.74-1.84, P = 0.495), and vitamin E (OR = 0.61, 95 % CI, 0.30-1.25, P = 0.180). Higher serum zinc can decrease the risk of vitiligo based on sensitivity analysis of the results. (OR = 0.29, 95 % CI 0.15-0.54, P < 0.001). Higher serum selenium level significantly increased the risk of vitiligo (OR = 4.31, 95 % CI, 2.72-6.81, P < 0.001). Vitamin A was not significantly different in two reported groups (6.35 ±â€¯1.53 vs 6.77 ±â€¯1.46 µg/mL, P > 0.05). Copper was significantly higher in vitiligo patients compared to controls (129 ±â€¯33 vs 99 ±â€¯19 µg /100 mL, P = 0.002). CONCLUSION: The current meta-analysis of data on serum level of most studied antioxidants (vitamin C, vitamin E, zinc and selenium) in patients suffering vitiligo showed that higher serum selenium (OR = 4.31) and lower zinc level (OR = 0.29) can increased the risk of vitiligo. Potential mechanism associated with preventive effects of zinc and the depigmentation effect of selenium should be more elucidated in further studies.

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.

Lack of association of IL-10 (rs1800896) and IL-13 (rs1800925) with non-segmental vitiligo susceptibility in South Indian population.

BACKGROUND: Vitiligo is an autoimmune depigmentation disorder caused by multiple etiologies. Genetic polymorphisms in cytokine genes influence their expression and augment disease development. Analyzing the influence of genetic polymorphisms will help in better understanding of the complex etiopathogenesis of vitiligo. AIM: To study the influence of interleukin IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms on vitiligo risk in South Indian population. METHODS: Two hundred and sixty-four vitiligo patients and 264 controls were recruited in this study. Genotyping was done by quantitative PCR and plasma cytokine levels were measured by ELISA. RESULTS: Allele frequencies of IL-10 (rs1800896) and IL-13 (rs1800925) SNPs were observed to be equal in the groups. Mutant allele G of IL-10 (rs1800896) enhanced the familial inheritance of vitiligo (P < 0.0001, OR-25.1, 95% CI-7.64-82.7) and influenced the development of vulgaris type of vitiligo (P = 0.034, OR-1.83, 95% CI-1.07-3.13). Ancestral allele A of IL-10 (rs1800896) conferred protection against development of acrofacial vitiligo (P = 0.04, OR-0.56, 95% CI-0.33-0.95). Circulatory IL-10 levels in vitiligo patients were higher than controls (P < 0.0001). Individuals with genotype GG of IL-10 (rs1800896) had the highest circulatory levels of IL-10 (P < 0.0001). Among the genotypes of IL-13 (rs1800925) variant, none influenced the phenotype of nonsegmental vitiligo such as gender, family history, age of onset and types of vitiligo (P > 0.05). In addition, no difference was noted in the circulatory levels of IL-13 between patients and controls (P = 0.48). Within patients, CC genotype of IL-13 (rs1800925) was observed to enhance the circulatory IL-13 levels (P < 0.0001). LIMITATION: Replication group analysis in a larger multicentric cohort in future would validate further understanding of vitiligo susceptibility in South Indian ethnics. CONCLUSION: IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms did not confer risk to develop vitiligo in South Indian population.

Higher incidence of metabolic syndrome components in vitiligo patients: a prospective cross-sectional study.

BACKGROUND/OBJECTIVES: To investigate the association between vitiligo and metabolic syndrome. METHODS: A prospective cross-sectional study was conducted between 2014 and 2016. Study (n=155) and control groups (n=155) were evaluated for metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III and the International Diabetes Federation criteria. Study group was divided into three groups according to their vitiligo area severity index and vitiligo disease activity score values (Group 1: 6.89 for VASI score, Group A: -1-0, Group B: 1-2 and Group C: 3-4 for vitiligo disease activity score respectively). MetS rates according to both criteria were compared between the vitiligo disease activity score and vitiligo area severity index groups. RESULTS: Metabolic syndrome rates were 37.4% and 40% in the study group and 19.4% and 26.5% in the control group according to National CholesterolEducation Program Adult Treatment Panel III and International Diabetes Federation criteria, respectively (p<001 and p=0.011). Metabolic syndrome was more frequent in vitiligo area severity index Groups 2 and 3 compared to vitiligo area severity index Group 1, and in vitiligo disease activity score Group C compared to vitiligo disease activity score Groups A and B. STUDY LIMITATIONS: Single center experience, absence of more specific oxidative-stress markers and lack of long-term follow-up of the patients. CONCLUSIONS: Frequency of metabolic syndrome was higher in patients with non-segmental vitiligo and the rate was higher in active/severe form of the disease.

Higher incidence of metabolic syndrome components in vitiligo patients: a prospective cross-sectional study

Abstract Background/Objectives: To investigate the association between vitiligo and metabolic syndrome. Methods: A prospective cross-sectional study was conducted between 2014 and 2016. Study (n = 155) and control groups (n = 155) were evaluated for metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III and the International Diabetes Federation criteria. Study group was divided into three groups according to their vitiligo area severity index and vitiligo disease activity score values (Group 1: 6.89 for VASI score, Group A: −1-0, Group B: 1-2 and Group C: 3-4 for vitiligo disease activity score respectively). MetS rates according to both criteria were compared between the vitiligo disease activity score and vitiligo area severity index groups. Results: Metabolic syndrome rates were 37.4% and 40% in the study group and 19.4% and 26.5% in the control group according to National CholesterolEducation Program Adult Treatment Panel III and International Diabetes Federation criteria, respectively (p < 001 and p = 0.011). Metabolic syndrome was more frequent in vitiligo area severity index Groups 2 and 3 compared to vitiligo area severity index Group 1, and in vitiligo disease activity score Group C compared to vitiligo disease activity score Groups A and B. Study limitations: Single center experience, absence of more specific oxidative-stress markers and lack of long-term follow-up of the patients. Conclusions: Frequency of metabolic syndrome was higher in patients with non-segmental vitiligo and the rate was higher in active/severe form of the disease.