Vitexin protects melanocytes from oxidative stress via activating MAPK-Nrf2/ARE pathway.

INTRODUCTION: Vitiligo is the most common type of depigmented skin disease. Cellular oxidative stress caused by reactive oxygen species (ROS) has been implicated in the pathogenesis of vitiligo. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway plays an important role in melanocytes against hydrogen peroxide (H2O2) induced oxidative stress. In addition, vitexin may protect vitiligo by inhibiting oxidative stress and inflammation. OBJECTIVE: In the present study, we aimed to investigate the antioxidant effect of vitexin-activated mitogen-activated protein kinase (MAPK)-Nrf2/ARE axis in vitiligo. METHODS: MTT assay identified cell viability of human melanocyte PIG1. Cell apoptosis was evaluated by flow cytometry. Gene and protein expression levels were analyzed by quantitative real-time PCR (qPCR) and Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of inflammatory factors and ROS production. RESULTS: Vitexin inhibited H2O2-induced melanocyte apoptosis and promoted cell proliferation. Moreover, vitexin decreased expression of interleukin-1ß (IL-1ß), IL-17A, and ROS in melanocytes induced by H2O2. Subsequently, activation of MAPK-Nrf2/ARE signaling was readily induced by vitexin treatment, as evidenced by the upregulation of antioxidant genes including heme oxygenase 1 (HO-1) and superoxide dismutase (SOD). Knockdown of Nrf2 reversed the protective effect of vitexin on H2O2-induced melanocytes. And, knockdown of Nrf2 increased the expression of IL-1ß, IL-17A and ROS, and reduced HO-1 and SOD expression. CONCLUSIONS: Vitexin protected melanocytes from oxidative stress by activating MAPK-Nrf2/ARE signaling pathway. Our results suggested that the role of the Nrf2/ARE axis in the antioxidant defense of melanocytes, and the potential therapeutic strategy for vitiligo.

The catalase gene promoter and 5'-untranslated region variants lead to altered gene expression and enzyme activity in vitiligo.

BACKGROUND: Oxidative stress is considered to be the initial event in the course of vitiligo. The enzyme catalase (CAT) is mainly involved in cellular defence against oxidizing agents through detoxifying H2 O2 . OBJECTIVES: The aims were (i) to assess erythrocyte CAT enzyme activity and lipid peroxidation (LPO) levels as well as CAT mRNA expression in skin and blood; (ii) to investigate CAT gene promoter rs7943316, rs1001179, 5'-untranslated region rs1049982, and exon (rs17886350, rs11032709, rs17880442, rs35677492) polymorphisms; and (iii) to perform genotype/haplotype-phenotype correlation analyses in patients with vitiligo and controls from Gujarat. METHODS: CAT activity and LPO levels were measured spectrophotometrically. CAT mRNA levels were estimated using real-time polymerase chain reaction (PCR) by the SYBR Green method. Single-nucleotide polymorphism genotyping was performed using PCR-restriction fragment length polymorphism and amplification-refractory mutation system-PCR analyses. RESULTS: Patients with vitiligo showed significantly decreased CAT mRNA expression in lesional and nonlesional skin and in blood, with reduced CAT activity compared with that of controls. CAT -89A/T and -20T/C polymorphisms were significantly associated with patients, especially with active and generalized vitiligo, whereas no association was observed for -262G/A and exon polymorphisms. The A-262 T-89 C-20 haplotype with variant alleles was found to be associated with 6·4-fold risk of vitiligo. Genotype/haplotype-phenotype correlation analyses revealed that individuals with susceptible genotypes/haplotype for CAT -89A/T and -20T/C polymorphisms showed significantly decreased CAT mRNA/activity, and only -89A/T polymorphisms showed significantly increased LPO levels compared with wild-type genotypes/haplotype. CONCLUSIONS: The present study proposes the crucial role of CAT and its allelic variants in oxidative stress-mediated pathogenesis of vitiligo.

JAK inhibitors in dermatology: The promise of a new drug class.

New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase-signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.

Effect of different types of therapeutic trauma on vitiligo lesions.

New treatment modalities for vitiligo acting by changing certain cytokines and metalloproteinases are newly emerging. The aim of this work is to To assess the efficacy of trichloroacetic acid (TCA) chemical peel, dermapen, and fractional CO2 laser in treatment of stable non-segmental vitiligo and to detect their effects on IL-17 and MMP-9 levels. Thirty patients with stable vitiligo were recruited in a randomized controlled study. They were randomly categorized into three equal groups. Group 1: TCA peel, Group 2: dermapen machine, and Group 3: Fractional CO2 laser. Skin biopsies were taken from treated areas and from control areas for which MMP-9 and IL-17 tissue levels were measured using ELISA. The 30 vitiligo patients had low basal tissue MMP-9 levels and high baseline IL-17 tissue levels. As regards the three different used modalities, all of them caused rise in MMP-9 as well as IL-17 levels and almost their levels were much more elevated with repetition of the previously mentioned traumatic procedures. TCA 25% peel proved to be the most effective modality both clinically and laboratory and it can be used prior or with other conventional therapies in the treatment of vitiligo.

Analysis of Manganese Superoxide Dismutase and Glutathione Peroxidase 1 Gene Polymorphisms in Vitiligo.

Vitiligo is a hereditary/acquired progressive pigmentation disorder characterized by discoloration of skin as a result of melanocyte dysfunction. Recent studies have proposed that oxidant/antioxidant status plays an important role in vitiligo pathogenesis because of the toxic effects on melanocytes. In this study, we aimed to investigate possible associations of MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms with vitiligo with in Turkish population. The study group consists of 57 patients with vitiligo and 69 healthy controls. Genotyping is performed to identify MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms. The method used for genotyping was based on the PCR amplification and detection of polymorphisms by hybridization probes labeled with fluorescent dyes. Both the genotype and allele frequencies of MnSOD Ala-9Val (p = 0.817 and p = 0.553, respectively) and GPx1 Pro198Leu polymorphisms (p = 0.422 and p = 0.673, respectively) were not significantly different between vitiligo patients and the control group. Although no significant difference was found, this is the first report investigating the possible associations between the MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms in Turkish population. Further studies with large populations will be able to clarify the association better.

SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival.

Vitiligo is an acquired and progressive hypomelanotic disease that manifests as circumscribed depigmented patches on the skin. The aetiology of vitiligo remains unclear, but recent experimental data underline the interactions between melanocytes and other typical skin cells, particularly keratinocytes. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. Sirtuins (silent mating type information regulation 2 homolog) 1, well-known modulators of lifespan in many species, have a role in gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy ageing. In the literature there is no evidence for SIRT1 signalling in vitiligo and its possible involvement in disease progression. Here, biopsies were taken from the perilesional skin of 16 patients suffering from non-segmental vitiligo and SIRT1 signalling was investigated in these cells. For the first time, a new SIRT1/Akt, also known as Protein Kinase B (PKB)/mitogen-activated protein kinase (MAPK) signalling has been revealed in vitiligo. SIRT1 regulates MAPK pathway via Akt-apoptosis signal-regulating kinase-1 and down-regulates pro-apoptotic molecules, leading to decreased oxidative stress and apoptotic cell death in perilesional vitiligo keratinocytes. We therefore propose SIRT1 activation as a novel way of protecting perilesional vitiligo keratinocytes from damage.

Genetic polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and risk of vitiligo in Han Chinese populations: a genotype-phenotype correlation study.

BACKGROUND: Recent evidence has revealed an elevation of total homocysteine (tHcy) in patients with vitiligo. Methylenetetrahydrofolate reductase (MTHFR) is one of the main enzymes regulating homocysteine (Hcy) metabolism. Thus, polymorphisms of MTHFR could potentially contribute to the development of vitiligo by affecting MTHFR activity and tHcy levels. OBJECTIVES: To evaluate the potential association between MTHFR polymorphisms and vitiligo susceptibility. METHODS: In total, 1000 patients with vitiligo and 1000 age- and sex-matched controls were enrolled in this hospital-based case-control study. Two single-nucleotide polymorphisms of the MTHFR gene (rs1801133 C>T and rs1801131 A>C) were selected and genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR, respectively. The MTHFR activity concentration and tHcy level in serum were measured by enzyme-linked immunosorbent assay. RESULTS: We found that allele T of rs1801133 in the MTHFR gene was associated with a significantly reduced risk of vitiligo (adjusted odds ratio 0·58, 95% confidence interval 0·43-0·76, P < 0·001). In addition, the patients with vitiligo had a lower activity concentration of MTHFR and higher level of tHcy than the controls. Correlation between these markers and the risk of vitiligo was also observed. Furthermore, the individuals with a no-risk genotype (CT + TT) of rs1801133 and higher activity concentration of MTHFR or lower level of tHcy had a significantly decreased risk of vitiligo. CONCLUSIONS: Our data suggest that MTHFR gene polymorphisms may play a vital role in genetic susceptibility to vitiligo.

Association of the 389 C/T polymorphism of the catalase gene with susceptibility to vitiligo: a meta-analysis.

BACKGROUND: The 389 C/T polymorphism in the catalase gene, CAT, has been reported to be associated with the risk of vitiligo. AIM: To evaluate the association of the CAT 389 C/T polymorphism with susceptibility to vitiligo. METHODS: We undertook a literature search and included the relevant studies passing the selection criteria. After the relevant data were extracted from each study, we statistically analysed the strength of association between the CAT gene and vitiligo risk. RESULTS: In total, 7 relevant studies were identified, comprising 1531 patients with vitiligo and 1608 controls. The genotype distribution in the controls of all studies complied with Hardy-Weinberg equilibrium. After pooling all studies, the results indicated that the 389 C/T polymorphisms in CAT were not associated with the risk of vitiligo in Asians and Turks; however the CT genotype might be a genetic risk factor for susceptibility to vitiligo (OR = 1.77, 95% CI 1.30-2.43, P < 0.001) and the CC genotype might decrease the risk of vitiligo (OR = 0.63, 95% CI 0.47-0.86, P < 0.01) in western Europeans. CONCLUSIONS: The 389 C/T polymorphisms in the CAT gene may be associated with vitiligo in western Europeans. Further studies with larger sample sizes are warranted to confirm our findings.

Inherited catalase deficiency: is it benign or a factor in various age related disorders?

Hydrogen peroxide was - and is still - considered toxic for a wide range of living organisms. Oxidative stress occurs when there is an excess of pro-oxidants over antioxidants and it has been implicated in several diseases. Catalase is involved in hydrogen peroxide catabolism and is important in defense against oxidative stress. Acatalasemia means the inherited near-total deficiency of catalase activity, usually in reference to red cell catalase. Acatalasemia was thought at first to be an asymptotic disorder. In the absence of catalase, neither the Japanese, or Hungarian acatalasemics nor acatalasemic mice had significantly increased blood glutathione peroxidase activity. In animal models, catalase deficient tissues show much slower rates of removal of extracellular hydrogen peroxide. In catalase knock-out mice, a decreased hydrogen peroxide removing capacity and increased reactive oxygen species formation were reported. Hydrogen peroxide may cause methemoglobinemia in patients with catalase deficiency. During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia. Patients with inherited catalase deficiency, who are treated with uric acid oxidase (rasburicase) may experience very high concentrations of hydrogen peroxide and may suffer from methemoglobinemia and hemolysis. The high (18.5%) prevalence of diabetes mellitus in inherited catalase deficient individuals and the earlier (10 years) manifestation of the disease may be attributed to the oxidative damage of oxidant sensitive, insulin producing pancreatic beta-cells. Ninety-seven of 114 acatalasemics had diseases related to oxidative stress and aging. The oxidative stress due to catalase deficiency could contribute to the manifestation of diabetes while for the other diseases it may be one of the factors in their causations. In summary, inherited catalase deficiency is associated with clinical features, pathologic laboratory test results, age and oxidative stress related disorders. Rather than considering it a benign condition, it should be considered as a complicating condition for aging and oxidative stress.

Serum activity of DPPIV and its expression on lymphocytes in patients with melanoma and in people with vitiligo.

BACKGROUND: Dipeptidyl peptidase IV, a multifunctional serine protease, is implicated in regulation of malignant transformation, promotion and further progression of cancer, exerting tumor-suppressing or even completely opposite - tumor-promoting activities. The aim of present research was to determine the serum DPPIV activity, as well as the percentages of CD26+ lymphocytes, CD26+ overall white blood cells and the mean fluorescence intensity of CD26 expression on lymphocytes in patients with melanoma, people with vitiligo and in healthy controls. METHODS: The activity of DPPIV in serum was determined by colorimetric test. Expression of DPPIV (as CD26) on immunocompetent peripheral white blood cells was done using flow cytometry analysis. RESULTS: Data from our study show for the first time statistically significant decrease: in the serum DPPIV activity, in the percentage of CD26+ overall white blood cells and in the percentage of lymphocytes in patients with melanoma in comparison to healthy control people. In addition, significantly lower serum DPPIV activity was found in the group of patients with melanoma in relation to people with vitiligo too. CONCLUSION: This study indicates the need for exploring the cause and the importance of the disturbances in the serum DPPIV activity and in the CD26 expression on immunocompetent cells in complex molecular mechanisms underlying the development and progression of melanoma.

Study of clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo undergoing melanocyte transplantation.

BACKGROUND: Stability is considered the most important parameter before performing any melanocyte transplantation procedure in vitiligo; however, current criteria rely on the history given by the patients. OBJECTIVE: This study was undertaken to determine the clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo to facilitate better patient selection for melanocyte transplantation and to understand immunological mechanisms for disease activity. METHODS: Thirty-three patients with generalized vitiligo with < 10% body surface area involved were allocated to three clinical stability groups: Group 1 (stability > 3 months but < 1 year), Group 2 (≥ 1 year but < 2 years) and Group 3 (≥ 2 years). Melanocyte transplantation was done using suction blister epidermal grafting (SBEG) on a single patch. Blood was drawn for catalase estimation from all patients and from 10 healthy control subjects. A 3-mm punch biopsy was taken on the day of transplantation from the margin of the macule in the first five patients in each group for the immunohistochemistry of CD4, CD8, CD45RO, CD45RA and FoxP3. Those with ≥ 75% repigmentation at 6 months were labelled as responders. RESULTS: The success rate was 0% in Group 1, 37·5% in Group 2 and 77·8% in Group 3. The difference in the success rate between the groups was statistically significant (P = 0·005). The median period of stability was significantly higher in the responders compared with that in the nonresponders (P = 0·001). Catalase levels were not significantly different between patients in the three groups of cases and in controls, or between responders and nonresponders. Lesional CD8 cells were significantly higher in Group 1 compared with Group 3. The percentages of CD8 and CD45RO cells were significantly higher in the nonresponders compared with the responders. CONCLUSION: Along with clinical stability, the proportion of CD8 and CD45RO cells in skin biopsies might help to determine the stability of the disease and thereby predict the success of transplantation.

Mechanisms of spatial and temporal development of autoimmune vitiligo in tyrosinase-specific TCR transgenic mice.

Generalized vitiligo is thought to have an autoimmune etiology and has been correlated with the presence of CD8 T cells specific for melanocyte differentiation Ag. However, limited animal models for the disease have hampered its understanding. Thus, we generated TCR transgenic mice that recognize an epitope of the melanocyte protein, tyrosinase. These animals develop vitiligo with strikingly similar characteristics to the human disease. Vitiligo develops temporally and spatially, with juvenile lesions forming bilaterally in head and facial areas, and only arising later in the body of adult animals. Vitiligo is entirely dependent on CD8 T cells, whereas CD4 T cells exert a negative regulatory effect. Importantly, CD8 T cells can be pervasively present in the skin in the steady state without inducing vitiligo in most areas. This points to developmental differences in melanocyte susceptibility and/or immunological effector mechanisms over time, or in different body locations. Disease is strongly dependent on both IFN-gamma and CXCR3, whereas dependence on CCR5 is more limited, and both CCR4 and perforin are dispensable. Genetic ablation of CXCR3 or IFN-gamma also resulted in scarce CD8 T cell infiltration into the skin. Our results identify unexpected complexity in vitiligo development and point toward possible therapeutic interventions.

GILT accelerates autoimmunity to the melanoma antigen tyrosinase-related protein 1.

Melanocyte differentiation Ags, including tyrosinase-related protein (TRP) 1, are relevant to both autoimmune skin depigmentation (vitiligo) and tumor immunity, because they are expressed by both benign melanocytes and many malignant melanomas. Melanoma patients generate CD4(+) T cells that specifically recognize these proteins. TRP1 contains internal disulfide bonds and is presented by MHC class II molecules. Gamma-IFN-inducible lysosomal thiol reductase (GILT) facilitates the generation of class II-binding peptides by the endocytic reduction of protein disulfide bonds. We show in this study that GILT is required for efficient MHC class II-restricted processing of a TRP1 epitope in vitro and accelerates the onset of vitiligo in TRP1-specific TCR transgenic mice. The presence of GILT confers a small increase in the percentage of autoreactive T cells with an effector memory phenotype that may contribute to earlier disease onset. The onset of vitiligo is associated with a greater increase in the percentage of autoreactive T cells with an effector memory phenotype. Given that many self and tumor Ags have disulfide bonds and are presented on MHC class II, GILT is likely to be important in the pathogenesis of other CD4(+) T cell-mediated autoimmune diseases and for the development of effective cancer immunotherapy.

Catalase -262C>T polymorphisms in Hungarian vitiligo patients and in controls: further acatalasemia mutations in Hungary.

Catalase is the main regulator of hydrogen peroxide metabolism. In vitiligo patients there are conflicting data on its activity and no data on the effect of -262C>T polymorphism in the catalase gene. Blood catalase activity, -262C>T polymorphism and acatalasemia mutations were examined in 75 vitiligo patients and in 162 controls, in Hungary. We measured blood catalase activity and conducted analyses with PCR-SSCP, polyacrylamide gel electrophoresis and silver staining in combination with RFLP and nucleotide sequencing. Comparison of the wild (CC) genotype and the mutant (TT) genotype in the vitiligo patients revealed a non significant (P > 0.19) increase in blood catalase. Male controls with the CT genotype had significantly (P < 0.04) lower blood catalase activity than CC genotype controls. Female vitiligo patients with CC genotype had lower (P < 0.04) blood catalase than female controls. The frequency of wild genotype (CC) and C alleles is significantly (P < 0.04) decreased in Hungarian controls when compared to controls in Slovenia, Morocco, UK, Greece, Turkey, USA, China. The detection of a novel acatalasemia mutation (37C>T in exon 9) and the 113G>A (exon 9) mutation in Hungary are further proofs of genetic heterogeneity origin of acatalasemia mutations. In conclusion, the -262 C>T polymorphism has a reverse effect on blood catalase in vitiligo patients and in controls. In controls the mutant genotypes and alleles are more frequent in Hungary than in several other populations. The new acatalasemia mutations are further examples of heterogeneity of acatalasemia.

Anti-oxidant defence mechanism in vitiliginous skin increases with skin type.

BACKGROUND: Vitiligo skin shows different burning capacity in people with different phototype. In normal skin antioxidant status is correlated to skin phototype, but unexpectedly it appears that there is a gradual decrease in burning susceptibility of depigmented skin of individuals with increasing phototype (II→VI). OBJECTIVE: To assess if the antioxidant response in the lesional vitiligo skin is involved in those protection mechanisms. Moreover, a possible correlation between cutaneous and systemic endogenous antioxidants in vitiligo patients has been investigated. METHODS: We enrolled in the study 29 patients with active vitiligo, divided into five groups according to skin type (II to VI). We analysed reduced and oxidized glutathione (GSH and GSSG, respectively), ubiquinone (CoQ10), catalase (Cat), superoxide dismutases (Cu/Zn-SOD and Mn-SOD), GSH peroxidase (GSH-Px), as indexes of chemical and enzymatic antioxidants, in suction blister roofs as well as in peripheral blood mononuclear cells (PBMNCs). RESULTS: The vitiligo patients showed an imbalance of antioxidant network, both in depigmented skin and PBMNCs. Interestingly, in vitiligo skin a phototype-related increase of antioxidant enzyme activities (Cat, Mn-SOD and GPx) and GSH amount have been observed. Similarly in PMBNCs Cat and total SOD activities, as well as GSH content progressively increased from skin type II to skin type VI. Endogenous antioxidants in vitiligo skin are correlated to those in PBMNCs, suggesting that systemic and epidermal antioxidant network functionalities are connected. CONCLUSIONS: The correlation between antioxidant levels and clinical phototype confirmed the hypothesis that other factors than melanin determine largely the minimal erythema dose values in vitiligo lesional skin.

Autoantibodies against tyrosine hydroxylase in patients with non-segmental (generalised) vitiligo.

Vitiligo is an acquired idiopathic hypomelanotic skin disorder characterised by depigmented macules because of loss of cutaneous melanocytes. Although the exact cause of vitiligo remains obscure, evidence suggests that autoimmunity plays a role in the pathogenesis of the disease. Previously, tyrosine hydroxylase (TH) was identified as a putative autoantigen in vitiligo using phage-display technology. In this study, the prevalence of TH antibodies in patients with vitiligo was investigated. A radioimmunoassay (RIA) was used to detect TH antibodies in sera from patients with either non-segmental vitiligo (n=79), segmental vitiligo (n=8) or other autoimmune diseases without concomitant vitiligo (n=91). Sera from healthy individuals (n=28) were also tested. Patients with segmental vitiligo, healthy controls and patients with other autoimmune diseases without concomitant vitiligo were all negative for TH antibody reactivity. Of 79 patients with non-segmental vitiligo, 18 (23%) were positive for TH antibodies in the RIA, and a significant increase in the prevalence of TH antibodies in patients with non-segmental vitiligo was evident when compared with controls (P=0.003). TH antibody prevalence was also significantly elevated in patients with active vitiligo compared to those with stable disease (P=0.009). Overall, the results indicate that TH is an antibody target in non-segmental but not in segmental vitiligo and that TH antibodies appear to be more frequent in patients with active vitiligo.

Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo.

To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP. Similarly, expression of heme oxygenases was followed in skin from vitiligo patients before and after PUVA treatment. Single and double immunostainings were used in combination with light and confocal microscopic analysis and Western blotting. Melanocyte expression of heme oxygenase 1 is upregulated, whereas heme oxygenase 2 is reduced in response to UV and 4-TBP. Upregulation of inducible heme oxygenase 1 was also observed in UV-treated explant cultures, in skin of successfully PUVA-treated patients and in melanocytes cultured from vitiligo non-lesional skin. Heme oxygenase encoding genes were subsequently cloned to study consequences of either gene product on cell viability, demonstrating that HO-1 but not HO-2 overexpression offers protection from stress-induced cell death in MTT assays. HO-1 expression by melanocytes may contribute to beneficial effects of UV treatment for vitiligo patients.

The polymorphism of catalase T/C codon 389 in exon 9 and vitiligo susceptibility: a meta-analysis.

BACKGROUND: The exact aetiology of vitiligo has not yet been established. Oxidative stress is involved in the pathophysiology of vitiligo. It has been described that some polymorphisms in the catalase (CAT) gene may affect the risk of vitiligo. However, the results were inconsistent. OBJECTIVE: We performed a meta-analysis of the published studies to derive a more precise estimate of the association between CAT T/C at codon 389 in exon 9 polymorphisms and vitiligo risk. METHODS: The PubMed, Medline, Cochrane Library, China National Knowledge Infrastructure (CNKI) databases were searched to identify relevant published studies. RESULTS: Four case-control studies (cases, 645; controls, 689) that investigated the association between C/T polymorphisms of CAT exon 9 and the risk of vitiligo were retrieved and analysed. Our findings suggested a significant association between the CAT T/C exon 9 polymorphism and vitiligo risk (CT + TT vs. CC pooled odds ratio, 1.43; 95% confidence interval, 1.14-1.80; P = 0 .002). CONCLUSION: We found a significant correlation between the CAT T/C exon 9 polymorphism and the risk of vitiligo.

[Effect of zibuganshenfang on the expression and activity of tyrosinase on B16 cells].

OBJECTIVE: ZiBuGanShenFang (ZBGSF) is a traditional herbal formula, which has showed an outstanding therapeutic effect on vitiligo clinically. Our aim is to investigate the influence of ZBGSF drug serum on the expression and activity of Tyrosinase in B16 cells, explore the mechanism of ZBGSF on Vitiligo treatment further. METHOD: tyrosinase activity was measured by zymological methods, western blotting and RT-PCR were used to measure the protein content and mRNA level of tyrosinase and related proteins, respectively. RESULT: ZBGSF drug serum had no effect on the proliferation of B16 cells. But it could promote Tyrosinase activity significantly and increase protein content and mRNA level of tyrosinase and related proteins in B16 cells. CONCLUSION: Promoting the expression of tyrosinase protein and mRNA may be the elementary basis of ZBGSF on Vitiligo treatment.