Glutathione Peroxidase Level in Patients with Vitiligo: A Meta-Analysis

Xiao, Bi-huan; Shi, Meihui; Chen, Hongqiang; Cui, Shaoshan; Wu, Yan; Gao, Xing-Hua; Chen, Hong-Duo

doi:https://doi.org/10.1155/2016/3029810

BioMed Research International

On this page

Abstract Introduction Materials and Methods Results Discussion Acknowledgments References Copyright Related Articles

Review Article Corrigendum

!

A Corrigendum for this article has been published. To view the article details, please click the ‘Corrigendum’ tab above.

Review Article | Open Access

Volume 2016 | Article ID 3029810 | https://doi.org/10.1155/2016/3029810

Glutathione Peroxidase Level in Patients with Vitiligo: A Meta-Analysis

Bi-huan Xiao,¹Meihui Shi,¹Hongqiang Chen,²Shaoshan Cui,³Yan Wu,¹Xing-Hua Gao,¹and Hong-Duo Chen¹

Academic Editor: Davinder Parsad

Received25 Dec 2015

Revised18 Mar 2016

Accepted05 Apr 2016

Published27 Apr 2016

Abstract

Abnormality of glutathione peroxidase (GPx) is involved in the etiology and pathogenesis of vitiligo. However, the results were controversial. Aim. The purpose of this meta-analysis is to compare the levels of GPx between vitiligo patients and healthy controls. Methods. Relevant published articles were searched according to eligibility criteria. A meta-analysis was conducted to pool estimates of the standardized mean difference (SMD) with 95% confidence interval (CI). Results. Twenty-three studies with a total of 1076 vitiligo patients and 770 healthy controls were included. The pooled meta-analysis showed that patients with vitiligo had equivalent levels of GPx with the healthy controls (SMD = −0.47, 95% CI: −1.03 to 0.08, and ). Further subgroup analysis showed that the GPx levels of Asian patients or segmental vitiligo patients were, respectively, lower than those of healthy controls (Asian: SMD = −0.47, 95% CI: −1.08 to 0.14, and ; segmental: SMD = −3.59, 95% CI: −6.38 to −0.80, and ). Furthermore, the GPx levels in serum/plasma were significantly decreased in either stable or active vitiligo patients, comparing to healthy controls (stable: SMD = −2.01, 95% CI: −3.52 to −0.49, and ; active: SMD = −2.34, 95% CI: −4.07 to −0.61, and ). Conclusion. This meta-analysis showed a significant association between low GPx level and vitiligo.

1. Introduction

Vitiligo is an idiopathic, acquired pigmentation disorder of skin and/or mucosa, with clinical manifestations of porcelain white patches. It is considered to be a multifactorial and polygenic disease caused by the destruction of melanocytes [1]. Amongst others, oxidative stress is considered to be one of the causative factors in the pathogenesis of vitiligo [2].

Glutathione peroxidase (GPx) is the general name of an enzyme family with peroxidase activity. It protects cells from oxidative damage through decreasing lipid hydroperoxides to their corresponding alcohols or reducing free hydrogen peroxide to water [3]. In vitiligo, many researches about this antioxidant marker have been sought, but the conclusions were conflicting. Some researchers reported elevated level, whereas others showed no change or reduced level. Due to the inconsistent results, we do the meta-analysis to clarify the GPx level in vitiligo patients.

2. Materials and Methods

2.1. Search Strategy

The PubMed, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang Med Online were searched by two independent investigators using the search terms (“vitiligo”) and (“glutathione peroxidase” or “GPx” or “GSH-Px” or “oxidant” or “antioxidant”). Additional potential relevant articles were further retrieved through a manual search of references from original reports. The research dated from the earliest time to December 2015.

2.2. Eligibility Criteria and Excluded Studies

We sought existing studies published in English or Chinese. Articles were included in this meta-analysis if (1) the case group consisted of vitiligo patients and the control group included healthy individuals and (2) the outcome measures reported quantitative GPx level (mean ± standard deviation). After reading the title and abstract, we excluded a study if it (1) was an animal or in vitro experiment, (2) was a case report or a review, and (3) consisted of duplicate data with other study. All studies were deliberately reviewed by two investigators to decide whether to be included.

2.3. Data Extraction

Two investigators independently screened studies for eligible articles. The following items including the first author, year of publication, nation, sample size, sources, test method of GPx, GPx estimated value, unit, type, and stage of vitiligo were extracted. If there were discrepancies, they would reach a consensus through discussion and reexamination or seeking help to a third investigator.

2.4. Quality Assessment

To estimate the quality of included studies, the Newcastle-Ottawa Scale (NOS) criteria were used by two investigators independently [4]. The NOS criteria were scored based on three aspects: (1) subject selection, 0~4, (2) comparability of subject, 0~2, and (3) clinical outcome, 0~3. Total NOS scores range from 0 (the lowest) to 9 (the highest). Any discrepancy between the two investigators on NOS scores of the enrolled studies was resolved by discussion or consultation with a third investigator.

2.5. Statistical Analysis

The standard mean difference (SMD) for the effect and corresponding 95% CIs were calculated from the original data of the appropriate studies in fixed effects model (Mantel-Haenszel method) or random-effects model (DerSimonian and Laird method). The random-effects model was applied when heterogeneity existed among studies, while the fixed effects model was applied when there was no statistical heterogeneity. In order to test for comparability, heterogeneity across the included studies was evaluated by Cochran test and test [5]. Subgroup meta-analyses were conducted according to race (Caucasian versus Asian), stage (active or stable), type (segmental or nonsegmental), or source of sample. The funnel plot was constructed to assess the effect of publication bias on the validity of the estimates. The symmetry of the funnel plot was further evaluated by Egger’s linear regression test [6]. All tests were two-sided, and a value of < 0.05 was regarded as statistically significant. Stata version 11.0 software (StataCorp., College Station, TX, USA) was performed for statistical analysis.

3. Results

3.1. Eligible Studies

We identified 215 studies according to search strategy as shown in Figure 1. After carefully reviewing and screening, 23 articles [3, 7–28] were finally included in the meta-analysis. The characteristic and methodological qualities of these studies were shown in Table 1. The overall study quality ranged from 5 to 7 stars. Of the 23 studies, the sample resource of 20 studies was either serum, plasma, erythrocyte, blood, skin, or blister fluid, and other 3 studies, respectively, tested the GPx level in two sample sources. So the total number of comparisons used in the meta-analysis was 26. The race of all included studies was Caucasian or Asian population. The levels of GPx stratified by sample sources and races were listed in Table 2.

3.2. The Levels of GPx in Vitiligo Patients and Healthy Controls

Random-effects model was applied to the pooled meta-analysis, as statistical heterogeneity existed among studies (, , and = 96.6%). The results indicated that patients with vitiligo had equivalent levels of GPx with the healthy controls (SMD = −0.47, 95% CI: −1.03 to 0.08, and ) (Figure 2).

Further subgroup analysis stratified by sample sources indicated that vitiligo patients had higher GPx levels than controls in skin (SMD = 1.49, 95% CI: 0.06 to 2.91, and ) and lower GPx levels than controls in blood (SMD = −1.06, 95% CI: −2.06 to −0.06, and ). No difference was seen in the source of serum (SMD = −1.24, 95% CI: −2.79 to 0.31, and ), plasma (SMD = −0.05, 95% CI: −1.43 to 1.34, and ), erythrocyte (SMD = −0.97, 95% CI: −1.94 to 0.00, and ), or blister fluid (SMD = −0.29, 95% CI: −1.56 to 0.98, and ) (Figure 3(a)). The analysis stratified by race indicated that vitiligo patients in Asian populations had lower GPx levels than controls (SMD = −0.47, 95% CI: −1.08 to 0.14, and ), but no difference was shown in Caucasian populations (SMD = 0.259, 95% CI: −0.28 to 0.80, and ) (Figure 3(b)). Five articles were included in the subgroup analyses stratified by stage and sample source of serum/plasma (Table 3). The results indicated that the vitiligo patients at either stable stage or active stage had lower GPx levels in serum/plasma compared to controls (stable: SMD = −2.01, 95% CI: −3.52 to −0.49, and ; active: SMD = −2.34, 95% CI: −4.07 to −0.61, and ) (Figures 4(a) and 4(b)). No significant difference was observed between stable stage and active stage (SMD = 0.50, 95% CI: −0.02 to 1.01, and ). Three articles were included in the subgroup analyses stratified by vitiligo type (Table 4). Segmental vitiligo patients had lower GPx levels compared to controls (SMD = −3.59, 95% CI: −6.38 to −0.80, and ). No significant difference was observed between nonsegmental vitiligo patients and controls (SMD = −2.81, 95% CI: −5.71 to 0.10, and ) or between segmental and nonsegmental vitiligo patients (SMD = −0.18, 95% CI: −0.47 to 0.11, and ).

(a)

(b)

(a)

(b)

3.3. Metaregression and Sensitivity Analyses

Univariate and multivariate metaregression analyses were used to explore possible sources of heterogeneity. The results showed that race could be the major source of heterogeneity (Table 5). The results of sensitivity analysis suggested that no individual studies significantly affected the pooled results, indicating a statistically robust result (Figure 5).

3.4. Publication Bias

We used Egger’s test to estimate the possibility of publication bias. The results showed that there was no obvious evidence of publication bias (, ).

4. Discussion

Oxidative stress inducing vitiligo is based on the fact that some intermediates such as 3,4-dihydroxyphenylalanine (dopa), dopachrome, and 5,6-dihydroxyindole are created during melanin biosynthesis [29]. The final result of these changes results in the continuous increase of hydrogen peroxide (H₂O₂), which restrains the antioxidative enzyme activity leading to the destruction of melanocytes [30]. Therefore, antioxidants are important to nullify the harmful radical-mediated reactions. GPx is a group of antioxidative markers against free radicals by detoxification and has been considered to be involved in the pathogenesis of many skin diseases [31–33]. Our meta-analysis investigated whether GPx is involved in the development of vitiligo. The results of included articles involving 26 comparisons on the relationship of GPx and vitiligo were controversial; that is, respective 50%, 31%, and 19% comparisons showed lower, equal, and higher levels in vitiligo samples. The difference may relate to the variations in the population race, disease type, activity, duration, sample sources, or detection method.

Till now, no meta-analysis has reported the association between the GPx level and vitiligo. The pooled meta-analysis results of all the comparisons indicated that the GPx levels in vitiligo patients were similar to healthy controls. As statistical heterogeneity existed among studies, we did further subgroup analysis. The results indicated a significant relationship between low GPx level and vitiligo incidence.

Our subgroup analysis showed that Asian vitiligo patients showed lower levels of GPx than the controls, but no difference was shown between Caucasian populations and healthy controls. The metaregression results, which showed that race could be the major source of heterogeneity of pooled meta-analysis, supported the above subgroup analysis results. The majority of previous studies have used serum or plasma to measure oxidant or antioxidant levels. In the present meta-analysis, whatever stable vitiligo patients or active vitiligo patients had lower serum/plasma levels of GPx than the controls. The patients with segmental type also had decreased GPx levels comparing to healthy controls. These results suggested that low GPx level may contribute to the pathogenesis of vitiligo in Asian population, unlike Caucasian population. The low level in serum/plasma was associated with vitiligo incidence, at whatever active stage or stable stage, especially in segmental vitiligo. Oxidative stress induced accumulation of toxic-free radicals may have a pathophysiologic role in the initiation and progression of vitiligo [2]. Reactive oxygen species (ROS) are scavenged by antioxidant defence mechanisms. Depletion of the endogenous antioxidants including GPx can overwhelm antioxidant defence mechanisms, resulting in oxidative stress medicated vitiligo. Besides, allelic variants in GPx gene may be associated with low levels of GPx activity [34, 35]. One previous study indicated that GPx polymorphism may contribute to the reduced GPx activity and the prevalence of vitiligo in Gujarat population [36].

In conclusion, this meta-analysis showed a significant association between low GPx level and vitiligo for Asian population or segmental patients. The low level in serum/plasma was associated with vitiligo incidence, at whatever active or stable stage. Nonetheless, the conclusion could not be completely confirmed as there are some limitations. The limited number, small sample sizes of studies, and methodological diversities may weaken the statistical power. More large-sample studies of higher quality should be done to verify the conclusions.

Competing Interests

The authors have no commercial associations that might create competing interests in connection with the submitted paper.

Acknowledgments

This work has been supported by National Natural Science Fund (code: 81301388) and Liaoning Province Education Bureau Project (code: LZ2015077).

References

R. M. Halder and J. L. Chappell, “Vitiligo update,” Seminars in Cutaneous Medicine and Surgery, vol. 28, no. 2, pp. 86–92, 2009.
View at: Publisher Site | Google Scholar
K. U. Schallreuter, J. M. Wood, and J. Berger, “Low catalase levels in the epidermis of patients with vitiligo,” The Journal of Investigative Dermatology, vol. 97, no. 6, pp. 1081–1085, 1991.
View at: Publisher Site | Google Scholar
H. Zedan, A. A. L. Abdel-Motaleb, N. M. A. A. Kassem, H. A. H. A. Hafeez, and M. R. E. A. Hussein, “Low glutathione peroxidase activity levels in patients with vitiligo,” Journal of Cutaneous Medicine and Surgery, vol. 19, no. 2, pp. 144–148, 2015.
View at: Publisher Site | Google Scholar
A. Stang, “Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses,” European Journal of Epidemiology, vol. 25, no. 9, pp. 603–605, 2010.
View at: Publisher Site | Google Scholar
J. L. Peters, A. J. Sutton, D. R. Jones, K. R. Abrams, and L. Rushton, “Comparison of two methods to detect publication bias in meta-analysis,” The Journal of the American Medical Association, vol. 295, no. 6, pp. 676–680, 2006.
View at: Publisher Site | Google Scholar
E. Zintzaras and J. P. A. Ioannidis, “HEGESMA: genome search meta-analysis and heterogeneity testing,” Bioinformatics, vol. 21, no. 18, pp. 3672–3673, 2005.
View at: Publisher Site | Google Scholar
B. Barikbin, S. Kavand, M. Yousefi, M. Hedayati, and M. Saeedi, “No differences in serum selenium levels and blood glutathione peroxidase activities in patients with vitiligo compared with healthy control subjects,” Journal of the American Academy of Dermatology, vol. 64, no. 2, pp. 444–445, 2011.
View at: Publisher Site | Google Scholar
I. C. Ozturk, K. Batcioglu, F. Karatas, E. Hazneci, and M. Genc, “Comparison of plasma malondialdehyde, glutathione, glutathione peroxidase, hydroxyproline and selenium levels in patients with vitiligo and healthy controls,” Indian Journal of Dermatology, vol. 53, no. 3, pp. 106–110, 2008.
View at: Publisher Site | Google Scholar
J. Zhao, W. Li, and S. Y. Li, “The detection of hydrogen peroxide, catalase and glutathion peroxide in serum of vitiligo,” Chinese Journal of Dermatology and Venereology, vol. 25, no. 10, pp. 739–740, 2011.
View at: Google Scholar
J. P. Chen, C. Y. Zhong, and Y. P. Kang, “Serum antioxidative enzyme and lipid peroxide in vitiligo patients,” Zhejiang Journal of Laboratory Medicine, vol. 9, no. 3, pp. 24–25, 2011.
View at: Google Scholar
H. Y. Ma, X. N. Ni, and G. S. Xue, “Detection of glutathione and glutathione peroxidase in the sera of patients with vitiligo,” Journal of Clinical Dermatology, vol. 30, no. 1, pp. 22–23, 2001.
View at: Google Scholar
F. Wang and H. Q. Xu, “Some enzymes and microelements change research in sera and tissue of vitiligo patients,” Chinese Journal of Dermatology and Venereology, vol. 7, no. 3, pp. 142–143, 1993.
View at: Google Scholar
K. Batçioğlu, E. Haznecı, Ç. Öztürk, A. B. Karabulut, and N. Karadağ, “The skin and plasma antioxidant enzyme activities in patients with vitiligo,” Trakya Üniversitesi Tıp Fakültesi Dergisi, vol. 27, no. 4, pp. 354–357, 2010.
View at: Google Scholar
E. Hazneci, A. B. Karabulut, Ç. Öztürk et al., “A comparative study of superoxide dismutase, catalase, and glutathione peroxidase activities and nitrate levels in vitiligo patients,” International Journal of Dermatology, vol. 44, no. 8, pp. 636–640, 2005.
View at: Publisher Site | Google Scholar
Z. P. Zeng, B. Z. Lin, and T. H. Ge, “A comparative study of oxidation and antioxidant capacity of skin and serum in patients with vitiligo,” Journal of Dermatology and Venereology, vol. 37, no. 3, pp. 140–142, 2015.
View at: Google Scholar
Z. J. Liu, J. Liu, and X. H. Tang, “Related parameters of oxidation and antioxidation in sera of vitiligo patients,” The Chinese Journal of Dermatovenereology, vol. 25, no. 4, pp. 255–257, 2011.
View at: Google Scholar
N. Karsli, C. Akcali, O. Ozgoztasi, N. Kirtak, and S. Inaloz, “Role of oxidative stress in the pathogenesis of vitiligo with special emphasis on the antioxidant action of narrowband ultraviolet B phototherapy,” The Journal of International Medical Research, vol. 42, no. 3, pp. 799–805, 2014.
View at: Publisher Site | Google Scholar
D. Ines, B. Sonia, B. M. Riadh et al., “A comparative study of oxidant-antioxidant status in stable and active vitiligo patients,” Archives of Dermatological Research, vol. 298, no. 4, pp. 147–152, 2006.
View at: Publisher Site | Google Scholar
M. Yildirim, V. Baysal, H. S. Inaloz, D. Kesici, and N. Delibas, “The role of oxidants and antioxidants in generalized vitiligo,” The Journal of Dermatology, vol. 30, no. 2, pp. 104–108, 2003.
View at: Publisher Site | Google Scholar
A. Jain, J. Mal, V. Mehndiratta, R. Chander, and S. K. Patra, “Study of oxidative stress in vitiligo,” Indian Journal of Clinical Biochemistry, vol. 26, no. 1, pp. 78–81, 2011.
View at: Publisher Site | Google Scholar
A. Jalel and M. H. Hamdaoui, “Study of total antioxidant status and glutathione peroxidase activity in Tunisian vitiligo patients,” Indian Journal of Dermatology, vol. 54, no. 1, pp. 13–16, 2009.
View at: Publisher Site | Google Scholar
E. M. Shajil and R. Begum, “Antioxidant status of segmental and non-segmental vitiligo,” Pigment Cell Research, vol. 19, no. 2, pp. 179–180, 2006.
View at: Publisher Site | Google Scholar
M. L. Ha, “Peripheral blood free radical level changes of vitiligo patients,” Shanghai Journal of Immunology, vol. 18, no. 1, pp. 46–47, 1998.
View at: Google Scholar
I. Dammak, S. Boudaya, F. Ben Abdallah, H. Turki, H. Attia, and B. Hentati, “Antioxidant enzymes and lipid peroxidation at the tissue level in patients with stable and active vitiligo,” International Journal of Dermatology, vol. 48, no. 5, pp. 476–480, 2009.
View at: Publisher Site | Google Scholar
M. Yildirim, V. Baysal, H. S. Inaloz, and M. Can, “The role of oxidants and antioxidants in generalized vitiligo at tissue level,” Journal of the European Academy of Dermatology and Venereology, vol. 18, no. 6, pp. 683–686, 2004.
View at: Publisher Site | Google Scholar
S. Passi, M. Grandinetti, F. Maggio, A. Stancato, and C. De Luca, “Epidermal oxidative stress in vitiligo,” Pigment Cell Research, vol. 11, no. 2, pp. 81–85, 1998.
View at: Publisher Site | Google Scholar
W. Li, S. Y. Li, and J. Q. Lu, “A comparative study on levels of oxidant-antioxidant in the tissue fluid from skin of vitiligo,” Chinese Journal of Dermatology and Venereology, vol. 26, no. 4, pp. 303–305, 2012.
View at: Google Scholar
Y. Xu, S. X. Yan, and Y. Hu, “Comparison of level of anti-oxidant enzyme and lipid peroxidation in the blister fluid from vitiligo lesions with that of normal skin,” Laboratory Medicine, vol. 19, no. 4, pp. 321–323, 2004.
View at: Google Scholar
S. K. Hann and W. Chun, “Autocytotoxic hypothesis for the destruction of melanocytes as the cause of vitiligo,” in Vitiligo: A Monograph on the Basic and Clinical Science, S. K. Hann and J. Nordlund, Eds., pp. 137–141, Blackwell Science, Oxford, UK, 2001.
View at: Google Scholar
D. Agrawal, E. M. Shajil, Y. S. Marfatia, and R. Begum, “Study on the antioxidant status of vitiligo patients of different age groups in Baroda,” Pigment Cell Research, vol. 17, no. 3, pp. 289–294, 2004.
View at: Publisher Site | Google Scholar
M. H. Javanbakht, M. Djalali, M. Daneshpazhooh et al., “Evaluation of antioxidant enzyme activity and antioxidant capacity in patients with newly diagnosed pemphigus vulgaris,” Clinical and Experimental Dermatology, vol. 40, no. 3, pp. 313–317, 2015.
View at: Publisher Site | Google Scholar
M. Naziroglu, M. Sahin, B. Cig, M. Aykur, I. Erturan, and Y. Ugan, “Hypericum perforatum modulates apoptosis and calcium mobilization through voltage-gated and TRPM2 calcium channels in neutrophil of patients with Behcet's disease,” The Journal of Membrane Biology, vol. 247, no. 3, pp. 253–262, 2014.
View at: Publisher Site | Google Scholar
H. M. Dutchak, “The protein oxidation and antioxidant defence mechanisms in children with atopic dermatitis,” Likars'ka Sprava/Ministerstvo Okhorony Zdorov'ia Ukrainy, no. 5, pp. 89–94, 2013.
View at: Google Scholar
Y. J. Hu and A. M. Diamond, “Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium,” Cancer Research, vol. 63, no. 12, pp. 3347–3351, 2003.
View at: Google Scholar
D. Ratnasinghe, J. A. Tangrea, M. R. Andersen et al., “Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk,” Cancer Research, vol. 60, no. 22, pp. 6381–6383, 2000.
View at: Google Scholar
S. Em, N. C. Laddha, S. C. hatterjee et al., “Association of catalase T/C exon 9 and glutathione peroxidase codon 200 polymorphisms in relation to their activities and oxidative stress with vitiligo susceptibility in Gujarat population,” Pigment Cell Research/Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society, vol. 20, no. 5, pp. 405–407, 2007.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2016 Bi-huan Xiao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

11065

Downloads

1241

Citations