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1.
Association between MnSOD Val16Ala Polymorphism and Cancer Risk: Evidence from 33,098 Cases and 37,831 Controls.
Wang, P, Zhu, Y, Xi, S, Li, S, Zhang, Y
Disease markers. 2018;:3061974
Abstract
Manganese superoxide dismutase (MnSOD) plays a critical role in the defense against reactive oxygen species. The association between MnSOD Val16Ala polymorphism and cancer risk has been widely studied, but the results are contradictory. To obtain more precision on the association, we performed the current meta-analysis with 33,098 cases and 37,831 controls from 88 studies retrieved from PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association. We found that the polymorphism was associated with an increased overall cancer risk (homozygous: OR = 1.09, 95% CI = 1.00-1.19; heterozygous: OR = 1.07, 95% CI = 1.02-1.12; dominant: OR = 1.08, 95% CI = 1.02-1.14; and allele comparison: OR = 1.06, 95% CI = 1.02-1.11). Stratification analysis further showed an increased risk for prostate cancer, Asians, Caucasians, population-based studies, hospital-based studies, low quality and high quality studies. However, the increased risk for MnSOD Val16Ala polymorphism among Asians needs further validation based on the false-positive report probability (FPRP) test. To summarize, this meta-analysis suggests that the MnSOD Val16Ala polymorphism is associated with significantly increased cancer risk, which needs further validation in single large studies.
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Association of the C47T polymorphism in superoxide dismutase gene 2 with noise-induced hearing loss: a meta-analysis.
Wang, J, Li, J, Peng, K, Fu, ZY, Tang, J, Yang, MJ, Chen, QC
Brazilian journal of otorhinolaryngology. 2017;(1):80-87
Abstract
INTRODUCTION Currently, there is limited information about the relationship between manganese superoxide dismutase (sod2) c47t polymorphism and susceptibility to noise-induced hearing loss (NIHL). OBJECTIVE The aim of this meta-analysis was to clarify the association between SOD2 C47T polymorphism and NIHL. METHODS A search in PubMed and Web of Science was performed to collect data. All full-text, English-written studies containing sufficient and complete case-and-control data about the relationship between SOD2 C47T polymorphism and NIHL were included. Three eligible studies, comprising 1094 subjects, were identified. pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated to evaluate the strength of the association between SOD2 C47T polymorphism and NIHL. RESULTS No significant association between C47T polymorphism and risk of NIHL was found with the following combinations: T vs. C (OR=0.83; 95% CI=0.63-1.09); TT vs. CC (OR=0.49; 95% CI=0.22-1.09); CT vs. CC (OR=0.54; 95% CI=0.25-1.17); TT vs. CC+CT (OR=0.82; 95% CI=0.50-1.32); CC vs. TT+TC (OR=0.49; 95% CI=0.23-1.04). However, in subgroup analysis, a significant association was found for TT vs. CC+CT (OR=0.77; 95% CI=0.42-1.41) in the Chinese population. CONCLUSION The present meta-analysis suggests that SOD2 C47T polymorphism is significantly associated with increased risk of NIHL in the Chinese population. Further large and well-designed studies are needed to confirm this association.
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Association between manganese superoxide dismutase (MnSOD) polymorphism and prostate cancer susceptibility: a meta-analysis.
Li, X, Shen, M, Cai, H, Liu, K, Liu, Y, Huang, Z, Liang, C, Deng, X, Ye, J, Zou, Q, et al
The International journal of biological markers. 2016;(4):e422-e430
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Abstract
BACKGROUND Previous studies have investigated the relationship between manganese superoxide dismutase (MnSOD) Val16Ala polymorphism and prostate cancer susceptibility, but the results have remained controversial. This meta-analysis was therefore performed to clarify this association. METHODS The databases PubMed, Embase and Web of Science were searched for relevant available studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Trial sequential analysis was used to reduce the risk of type I error and estimate whether the evidence of the results was sufficient. RESULTS Overall, a significant increased risk of prostate cancer was associated with MnSOD Val16Ala polymorphism for the heterozygote model (OR = 1.14; 95% CI, 1.05-1.24), homozygote model (OR = 1.18; 95% CI, 1.02-1.36), dominant model (OR = 1.24; 95% CI, 1.07-1.44) and recessive model (OR = 1.10; 95% CI, 0.96-1.24). In the subgroup analysis by genotyping method, the results were statistically significant for the TaqMan and PCR-RFLP methods. In addition, when stratified by sample size, statistically significant increased risks were found among both large samples and small samples. Furthermore, when stratified by source of control, significant results were detected in both population-based controls and hospital-based controls. By trial sequential analyses, these findings in the current study were shown to be based on sufficient evidence. CONCLUSIONS This meta-analysis indicated that the Ala allele of the MnSOD gene polymorphism increases prostate cancer susceptibility.
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Oxidative and Anti-Oxidative Stress Markers in Chronic Glaucoma: A Systematic Review and Meta-Analysis.
Benoist d'Azy, C, Pereira, B, Chiambaretta, F, Dutheil, F
PloS one. 2016;(12):e0166915
Abstract
Chronic glaucoma is a multifactorial disease among which oxidative stress may play a major pathophysiological role. We conducted a systematic review and meta-analysis to evaluate the levels of oxidative and antioxidative stress markers in chronic glaucoma compared with a control group. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies reporting oxidative and antioxidative stress markers in chronic glaucoma and in healthy controls using the following keywords: "oxidative stress" or "oxidant stress" or "nitrative stress" or "oxidative damage" or "nitrative damage" or "antioxidative stress" or "antioxidant stress" or "antinitrative stress" and "glaucoma". We stratified our meta-analysis on the type of biomarkers, the type of glaucoma, and the origin of the sample (serum or aqueous humor). We included 22 case-control studies with a total of 2913 patients: 1614 with glaucoma and 1319 healthy controls. We included 12 studies in the meta-analysis on oxidative stress markers and 19 on antioxidative stress markers. We demonstrated an overall increase in oxidative stress markers in glaucoma (effect size = 1.64; 95%CI 1.20-2.09), ranging from an effect size of 1.29 in serum (95%CI 0.84-1.74) to 2.62 in aqueous humor (95%CI 1.60-3.65). Despite a decrease in antioxidative stress marker in serum (effect size = -0.41; 95%CI -0.72 to -0.11), some increased in aqueous humor (superoxide dismutase, effect size = 3.53; 95%CI 1.20-5.85 and glutathione peroxidase, effect size = 6.60; 95%CI 3.88-9.31). The differences in the serum levels of oxidative stress markers between glaucoma patients and controls were significantly higher in primary open angle glaucoma vs primary angle closed glaucoma (effect size = 12.7; 95%CI 8.78-16.6, P < 0.001), and higher in pseudo-exfoliative glaucoma vs primary angle closed glaucoma (effect size = 12.2; 95%CI 8.96-15.5, P < 0.001). In conclusion, oxidative stress increased in glaucoma, both in serum and aqueous humor. Malonyldialdehyde seemed the best biomarkers of oxidative stress in serum. The increase of some antioxidant markers could be a protective response of the eye against oxidative stress.
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Meta-Analyses of Manganese Superoxide Dismutase Activity, Gene Ala-9Val Polymorphism, and the Risk of Schizophrenia.
Wang, DF, Cao, B, Xu, MY, Liu, YQ, Yan, LL, Liu, R, Wang, JY, Lu, QB
Medicine. 2015;(36):e1507
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Abstract
Schizophrenia is a complex and disabling psychiatric disorder, and tardive dyskinesia (TD) is a severe adverse drug effect occurring in 20% to 40% of schizophrenic patients chronically treated with typical neuroleptics. Previous studies suggested that the manganese superoxide dismutase (MnSOD) activity was associated with the development of schizophrenia. Ala-9Val polymorphism, a functional polymorphism of MnSOD gene, has been reported to be related to the risk of schizophrenia and TD. However, these studies did not lead to consistent results. We performed meta-analyses aiming to assess the association between MnSOD activity and schizophrenia, as well as the association of MnSOD Ala-9Val polymorphism with schizophrenia and TD in schizophrenic patients.We search for the literature on MnSOD and schizophrenia in English or Chinese published up to May 1, 2015 on PubMed, EMBASE, the Cochrane Databases, Chinese National Knowledge Infrastructure, China Biology Medical and Wanfang databases. Two investigators independently reviewed retrieved literature and evaluated eligibility. Discrepancy was resolved by consensus with a third reviewer. Data were pooled using fixed-effect or random-effect models. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for the MnSOD activity. Pooled odds ratio (OR) and 95% CI were calculated for Ala-9Val genotype and allele frequencies.There were 6, 6, and 10 studies entering 3 parts of meta-analyses, respectively. The MnSOD activity of patients was significantly lower than that of controls (SMD = -0.94; 95% CI: -1.76, -0.12; P = 0.025). No significant associations of Ala-9Val genotypes (OR = 1.14; 95% CI: 0.97, 1.33; P = 0.109) and alleles (OR = 1.06; 95% CI: 0.94, 1.20; P = 0.361) with the risk of schizophrenia were observed. We also did not reveal significant associations of the genotypes (OR = 0.82; 95% CI: 0.66, 1.02; P = 0.075) and alleles (OR = 0.90; 95% CI: 0.76, 1.06; P = 0.215) with the risk of TD in schizophrenia.The decreased MnSOD activity may be associated with the risk of chronic schizophrenia in Chinese population, while MnSOD Ala-9Val polymorphism may not play a significant role in the development of schizophrenia and TD. Longitudinal studies with larger sample sizes and different ethnicities are needed to confirm the association of the MnSOD Ala-9Val variants with schizophrenia and TD.
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Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis.
Jiménez-Fernández, S, Gurpegui, M, Díaz-Atienza, F, Pérez-Costillas, L, Gerstenberg, M, Correll, CU
The Journal of clinical psychiatry. 2015;(12):1658-67
Abstract
OBJECTIVE To investigate the role of oxidative stress and antioxidants in depression. DATA SOURCES We searched the literature without language restrictions through MEDLINE/PubMed, Cochrane Library, Fisterra, and Galenicom from database inception until December 31, 2013, supplemented by a hand search of relevant articles. Search terms included (1) oxidative stress, antioxidant*, nitrosative stress, nitrative stress, nitro-oxidative stress, free radical*, and names of individual oxidative stress markers/antioxidants and (2) depression and related disorders and antidepressant. STUDY SELECTION Included were studies in patients with depression comparing antioxidant or oxidative stress markers with those in healthy controls before and after antidepressant treatment. DATA EXTRACTION Two authors independently extracted the data for antioxidant or oxidative stress markers. Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) for results from ≥ 3 studies were calculated. DATA SYNTHESIS Altogether, 29 studies (N = 3,961; patients with depression = 2,477, healthy controls = 1,484) reported on the oxidative stress marker malondialdehyde (MDA) and total nitrites, the antioxidants uric acid and zinc, or the antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). When patients with depression were compared with healthy controls, depression was associated with higher oxidative stress MDA levels (8 studies; n = 916; SMD = 1.34; 95% CI, 0.57 to 2.11; P < .001), lower antioxidant uric acid (4 studies; n = 512; SMD = -0.64; 95% CI, -1.22 to -0.06; P = .030) and zinc levels (13 studies; n = 2,002; SMD = -0.66; 95% CI, -0.98 to -0.34; P < .0001), and higher antioxidant-enhancing enzyme SOD levels (11 studies; n = 902; SMD = 0.62; 95% CI, 0.07 to 1.17; P = .028), while differences in total nitrites and CAT and GPX were nonsignificant. Antidepressant treatment, which significantly reduced Hamilton Depression Rating Scale scores (24.6 ± 0.7 to 16.2 ± 1.6; SMD = 2.65; 95% CI, 1.13 to 4.15; P = .00065), reduced MDA (4 studies; n = 194; SMD = -1.45; 95% CI, -2.43 to -0.47; P = .004) and increased uric acid (3 studies; n = 212; SMD = 0.76; 95% CI, 0.03 to 1.49; P = .040) and zinc levels (3 studies; n = 65; SMD = 1.22; 95% CI, 0.40 to 2.04, P = .004), without differences in MDA (P = .60), uric acid (P = .10), and zinc (P = .163) levels compared to healthy controls. CONCLUSIONS Results suggest that oxidative stress plays a role in depression and that antidepressant activity may be mediated via improving oxidative stress/antioxidant function.
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Different association of manganese superoxide dismutase gene polymorphisms with risk of prostate, esophageal, and lung cancers: evidence from a meta-analysis of 20,025 subjects.
Sun, GG, Wang, YD, Lu, YF, Hu, WN
Asian Pacific journal of cancer prevention : APJCP. 2013;(3):1937-43
Abstract
Altered expression or function of manganese superoxide dismutase (MnSOD) has been shown to be associated with cancer risk but assessment of gene polymorphisms has resulted in inconclusive data. Here a search of published data was made and 22 studies were recruited, covering 20,025 case and control subjects, for meta- analyses of the association of MnSOD polymorphisms with the risk of prostate, esophageal, and lung cancers. The data on 12 studies of prostate cancer (including 4,182 cases and 6,885 controls) showed a statistically significant association with the risk of development in co-dominant models and dominant models, but not in the recessive model. Subgroup analysis showed there was no statistically significant association of MnSOD polymorphisms with aggressive or nonaggressive prostate cancer in different genetic models. In addition, the data on four studies of esophageal cancer containing 620 cases and 909 controls showed a statistically significant association between MnSOD polymorphisms and risk in all comparison models. In contrast, the data on six studies of lung cancer with 3,375 cases and 4,050 controls showed that MnSOD polymorphisms were significantly associated with the decreased risk of lung cancer in the homozygote and dominant models, but not the heterozygote model. A subgroup analysis of the combination of MnSOD polymorphisms with tobacco smokers did not show any significant association with lung cancer risk, histological type, or clinical stage of lung cancer. The data from the current study indicated that the Ala allele MnSOD polymorphism is associated with increased risk of prostate and esophageal cancers, but with decreased risk of lung cancer. The underlying molecular mechanisms warrant further investigation.
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Association of the C47T polymorphism in SOD2 with diabetes mellitus and diabetic microvascular complications: a meta-analysis.
Tian, C, Fang, S, Du, X, Jia, C
Diabetologia. 2011;(4):803-11
Abstract
AIMS/HYPOTHESIS A meta-analysis was performed to assess the association of C47T (rs4880) (also called Val16Ala) polymorphism in SOD2 gene with reduced risk of diabetes mellitus, including type 1 and type 2 diabetes, and diabetic microvascular complications (DMI) including diabetic nephropathy, diabetic retinopathy and diabetic polyneuropathy. METHODS A comprehensive search was conducted to identify all case-control or cohort design studies of the above-mentioned associations. The fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. Heterogeneity among studies was evaluated using the I (2). Meta-regression and the 'leave one out' sensitive analysis of Patsopoulos et al. were used to explore potential sources of between-study heterogeneity. Publication bias was estimated using modified Egger's linear regression test as proposed by Harbord et al. RESULTS Seventeen articles were included. After excluding articles that deviated from Hardy-Weinberg equilibrium in cases and/or in controls, and were also the key contributors to between-study heterogeneity, the meta-analysis showed a significant association of the C allele with reduced risk of DMI in dominant (OR 0.788, 95% CI 0.680-0.914), recessive (OR 0.808, 95% CI 0.685-0.953) and codominant (OR 0.828, 95% CI 0.751-0.913) models. It also showed a significant association with reduced risk of diabetic nephropathy in the dominant model (OR 0.801, 95% CI 0.664-0.967), and reduced risk of diabetic retinopathy in the dominant (OR 0.601, 95% CI 0.423-0.855), recessive (OR 0.548, 95% CI 0.369-0.814) and codominant (OR 0.651, 95% CI 0.517-0.820) models. CONCLUSIONS/INTERPRETATION The meta-analysis suggested that C allele of C47T polymorphism in SOD2 gene has protective effects on risk of DMI, diabetic nephropathy and diabetic retinopathy. This risk needs to be confirmed by further studies.
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Possible risk modifications in the association between MnSOD Ala-9Val polymorphism and breast cancer risk: subgroup analysis and evidence-based sample size calculation for a future trial.
Chen, Y, Pei, J
Breast cancer research and treatment. 2011;(2):495-504
Abstract
Manganese superoxide dismutase (MnSOD) has been identified as an important scavenger of reactive oxygen species (ROS), which can cause oxidative stress followed by breast cancer. A number of subsequent population-based studies have investigated the association between MnSOD Ala-9Val polymorphism and the risk of breast cancer. However, these studies have yielded conflicting results. This fact implies that the effect of MnSOD Ala-9Val polymorphism on the susceptibility to breast cancer may be modified by other risk factors. To provide a more definitive conclusion, a full meta-analysis combining and summarizing 16 studies was first performed using both traditional and Bayesian approaches. During this step, a recessive inheritance mode was determined after a biological justification. The capability of the Bayesian method was highlighted in the estimation of a pooled odds ratio and 95% confidence interval. As a result, no significant association was observed (OR = 0.978, CI = 0.914-1.046). Bayesian meta-regression and subgroup analysis were then conducted to find possible risk modifications by other factors, including menopausal status, ethnicity effect, use of oral contraceptives, use of hormone replacement therapy, fruits and vegetables intake, vitamin supplement, and body mass index. While the power of most subgroups may be insufficient to make a statistical statement, an evidence-based sample size calculation based upon updated meta-analysis was performed to power a future trial. For example, approximately 5,000 subjects are required for a new Asian study (2,500 cases and 2,500 controls) to achieve 80% power.
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MnSOD Val16Ala polymorphism and prostate cancer susceptibility: a meta-analysis involving 8,962 subjects.
Mao, C, Qiu, LX, Zhan, P, Xue, K, Ding, H, Du, FB, Li, J, Chen, Q
Journal of cancer research and clinical oncology. 2010;(7):975-9
Abstract
PURPOSE Published data on the association between manganese superoxide dismutase (MnSOD) Val(16)Ala polymorphism and prostate cancer (PCA) risk are inconclusive. To derive a more precise estimate of the association between them, a meta-analysis was performed. METHODS PubMed and Embase were searched. All eligible studies were retrieved. The pooled odds ratio (OR) with 95% confidence interval (CI) for PCA risk associated with Val/Ala versus Val/Val, Ala/Ala versus Val/Val, dominant model (Ala/Ala + Val/Ala vs. Val/Val), and recessive model (Ala/Ala vs. Val/Ala + Val/Val) were estimated, respectively. RESULTS A total of 12 studies including 8,962 subjects were involved in this meta-analysis. Overall, the meta-analysis indicated that significantly elevated cancer risk was associated with Ala variant genotype when all the eligible studies were pooled into the meta-analysis (for Val/Ala vs. Val/Val: OR = 1.11, 95% CI = 1.00-1.24; for Ala/Ala vs. Val/Val: OR = 1.22, 95% CI = 1.00-1.49; for dominant model: OR = 1.14, 95% CI = 1.03-1.26). In the subgroup analysis by ethnicity, statistically significant increased risks were found among Caucasians with Ala allele (for Val/Ala vs. Val/Val: OR = 1.12, 95% CI = 1.00-1.25; for dominant model: OR = 1.14, 95% CI = 1.02-1.26). However, no significant associations were found in Africans. CONCLUSIONS This meta-analysis suggests that the Ala allele of the MnSOD gene was a low-penetrance susceptible gene in PCA development, especially in Caucasians.