Manganese Superoxide Dismutase Val16Ala Research Articles

Association of manganese superoxide dismutase Ala16Val gene polymorphism with diabetic retinopathy risk in type 2 diabetes: A systematic review and meta-analysis

Association of manganese superoxide dismutase Ala16Val gene polymorphism with diabetic retinopathy risk in type 2 diabetes: A systematic review and meta-analysis

Association of MnSOD Val16Ala (rs4880) Polymorphism with Staging, Grading, and Molecular Profile of Breast Cancer Patients at Prof. Dr. I.G.N.G. Ngoerah Hospital Denpasar Bali

Background: Aging is the major risk factor for breast cancer. Aging and breast cancer are interrelated due to the accumulation of reactive oxygen species (ROS). Manganese superoxide dismutase (MnSOD) has a pivotal role to defense ROS. The MnSOD Val16Ala (rs4880) polymorphism affects the activity of MnSOD in ROS detoxification. This study aims to prove the association of MnSOD Val16Ala (rs4880) polymorphism with stage, grading, and molecular profile of breast cancer patients at Prof. Dr. I.G.N.G. Ngoerah Hospital Denpasar Bali. Methods: This study used a cross-sectional exploratory descriptive method. It was conducted at the Integrated Biomedical Laboratory Unit of the Faculty of Medicine, Udayana University from September to November 2022. The samples used in this study were 45 biological materials in the form of DNA from breast cancer patients who were treated at the Oncology Unit of Prof. Dr. I.G.N.G. Ngoerah Hospital from 2016 to 2018 which is stored in the Biochemistry Laboratory of the Faculty of Medicine, Udayana University. The MnSOD Val16Ala (rs4880) polymorphism was examined by DNA amplification using polymerase chain reaction (PCR) method and the identification of the polymorphism by sequencing. The results obtained were analyzed using descriptive analysis with SPSS program. Results: The sequencing results found 45 samples (100%) with homozygous wild-type T/T. The association between MnSOD Val16Ala (rs4880) polymorphism and staging, grading, and molecular profile was unable to analyze. Conclusions: The MnSOD Val16Ala (rs4880) polymorphism was not found in breast cancer patient in Prof. Dr. I.G.N.G. Ngoerah hospital, Denpasar, Bali. Further research is needed to understand the role of MnSOD Val16Ala (rs4880) polymorphism with breast cancer risk. Keywords: superoxide dismutase enzyme, polymorphism, breast cancer

Association between MnSOD Activity and Cognitive Impairment in Unmedicated First-Episode Schizophrenia: Regulated by MnSOD Ala-9Val Gene Polymorphism.

The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, MnSOD Ala-9Val polymorphism and cognitive dysfunction in unmedicated first-episode (UMFE) SZ patients, which has not been examined. We recruited 234 UMFE SZ patients and 232 healthy controls (HC) and evaluated them with Repeated Battery for the Assessment of Neuropsychological Status (RBANS), plasma MnSOD activity and MnSOD Ala-9Val (rs4880) polymorphism. In addition, we used the Positive and Negative Syndrome Scale (PANSS) to assess the severity of patients’ psychopathological symptoms. Compared with HC, UMFE patients showed extensive cognitive impairment on RBANS, and had higher MnSOD activity. MnSOD Ala-9Val polymorphism was not associated with SZ susceptibility and cognitive impairment, but only affected MnSOD activity in patients. Moreover, only in SZ patients with Val homozygotes, MnSOD activity was significantly correlated with cognitive impairment, especially in RBANS total score, visuospatial/constructional and attention index scores. Our results suggest that cognitive impairment is associated with MnSOD activity in patients with first-episode SZ, which may be regulated by MnSOD Ala-9Val polymorphism.

Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL-1β and IL-6 Pathways.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has been associated with different diseases. However, there are scarcely studies relating this SNP in epilepsy, a neurologic disease that involves some interacting pathways, such as apoptotic and inflammatory factors. In this sense, we decided to investigate the relationship of MnSOD Ala16Val SNP with apoptotic markers in epilepsy and its relation with inflammatory pathway and seizure type. Ninety subjects were evaluated (47 epilepsies; 43 controls) by questionnaires and laboratorial exams. We observed a higher percentage of VV genotype in the epilepsy group when compared to the control group. IL-1β, IL-6, caspase-1, and caspase-3 levels were increased in the epilepsy group (VV genotype). Furthermore, an important correlation between IL-1β vs. caspase-1 and IL-6 vs. caspase-3 was observed in the epilepsy group (VV genotype). The epilepsy group which presented generalized seizures also demonstrated a positive correlation between IL-1β vs. CASP1 and IL-6 vs. CASP3. Thus, it is a plausible propose that epilepsy patients with VV genotype and generalized seizures present a worse inflammatory and apoptotic status. Our findings suggest that the knowledge of MnSOD Ala16Val polymorphism existence is important to evaluate molecular mechanisms associated to seizure and improve the treatment of these patients.

National data on non-modifiable risk factors of coronary artery diseases in Egypt

Abstract Background CAD accounts for approximately 42% of all cardiovascular deaths. A lot of predisposing risk factors for CAD exist and they are generally divided into modifiable and non-modifiable risk factors. Genetic variants were found to be among the non-modifiable risk factors where they strongly contribute to the incidence of CAD in Egyptian populations. Purpose highlighting the different genetic polymorphisms and non-modifiable risk factors for CAD in Egyptians and ranking them according to the degree of importance. Methods Intensive research was done in the period between 15 May 2018 and 15 September 2018 on both Science Direct, SCOPUS and Pubmed with the keywords (((myocardial infarction) OR (myocardial ischemia) OR (MI) OR (coronary artery disease) OR (CAD)) AND ((risk) OR (risk factors)) AND ((Egypt) OR (Egyptian))). 1060 studies were retrieved. Three reviewers screened the results and chose 84, from which, only 7 studies from 7 different centers from different parts of Egypt shown on map were included after full text screening with total no of 523 of various coronary artery disease patients and 396 healthy matched controls. Exclusion criteria was as follows: Full text not available (only abstract or protocol is published)The study was not randomized with a risk of biased resultsThe presence of any other comorbid disease as renal failure and autoimmune diseasesThe absence of control group in the study. Inclusion criteria was as following: Randomized controlled studyCross sectional studiesMean age of the patients above 30 years oldStudy on Egyptian populationsFull text and results available Results The polymorphisms (TPA, PAI-1, Paraoxonase-1, Manganese superoxide dismutase Ala16Val polymorphism, Platelet derived growth factor B gene polymorphism, rs854560 PON1, rs1790349 and rs12785878 of NADSYN1/ DHCR7 Locus, rs10741657, rs2060793, rs1993116 and rs10766197 of CYP2R1) demonstrated a significant association with the incidence of CAD in the Egyptian population. The odds ratios (ORs) for the putatively at high risk homozygous genotype vs. other genotypic groups of the different polymorphisms are shown clearly in the figure 1. The highest association is recorded for SNP rs1993116 of the CYP2R1 gene (ORs 8.5), followed by manganese superoxide dismutase Ala16Val polymorphism (ORs 3.6). Conclusion Many SNPs were found to be associated with CAD incidence in Egyptians, on top of which lies the SNP rs1993116 of the CYP2R1 gene and manganese superoxide dismutase Ala16Val polymorphism

Role of MnSOD Val16Ala Gene Polymorphism in Changing the Level of Serum Metals in Workers Exposed to Heavy Metals in Al-Nasiriyah City

Low activity of antioxidant enzymes due to polymorphism in antioxidant genes and differences in mineral and metal levels creates oxidative stress that may play a role in advancing many diseases. The aim of this study was to determine the role of Manganese superoxide dismutase (MnSOD) gene polymorphism [rs4880 Val16Ala)] in exposed workers and to compare the levels of metals and minerals among its various genotypes in control group. A total of 80 individuals including age and gender matched workers and control group were genotyped. Detection of rs4880 polymorphism was done using sequencing technique. The blood serum were tested for determination of metals and minerals using Atomic absorption spectrophotometer (AA 6600 Shimadzu). This study indicate that the frequency of T allele was higher than that of C allele in control group as well as in workers. Our results indicate no association between all genotypes in study subjects. The results of present study indicates that Pb and Cd concentration differ significantly between TT genotypes of MnSOD (rs4880) gene polymorphism as compared to CC genotypes in workers and control group (p<0.05). Control group with TT, TC and CC genotypes have high concentration of Fe, Cu and Zn as compared to workers group.

The Influence of GPX1 Pro198Leu, CAT C262T and MnSOD Ala16Val Gene Polymorphisms on Susceptibility for Non-Hodgkin Lymphoma and Overall Survival Rate at Five Years from Diagnosis

Abstract Objective: The aim of the current study was to investigate possible associations between catalase C262T (CAT C262T), glutathione peroxidase 1 Pro198Leu (GPX1 Pro198Leu), manganese superoxide dismutase Ala16Val (MnSOD Ala16Val) gene polymorphisms and non-Hodgkin Lymphoma risk (NHL) in a Romanian population and the five-year overall survival rate of the NHL patients. Methods: We included in this case-control study 406 individuals, divided into two groups: the control group (n=315) and the patients group (n=91). The DNA was extracted from peripheral blood and amplified using specific techniques. Results: The variant homozygous genotype of GPX1 Pro198Leu represents a risk factor for NHL development and no associations regarding the risk for NHL were found for MnSOD Ala16Val and CAT C262T gene polymorphisms. Two of the studied polymorphisms were associated with the overall survival rate thus: negative association regarding MnSOD Ala16Val, associated with higher overall survival rate and a positive one regarding CAT C262T, associated with lower overall survival rate. Conclusions: According to our results, the mentioned polymorphisms may be considered as susceptible markers of the five-year overall survival rate for NHL patients. Future studies with a larger number of patients are needed to confirm our results.

Association between MnSOD Val16Ala Polymorphism and Cancer Risk: Evidence from 33,098 Cases and 37,831 Controls.

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.

The relationship between MnSOD Val16Ala gene polymorphism and the level of serum total antioxidant capacity with the risk of chronic kidney disease in type 2 diabetic patients: a nested case-control study in the Tehran lipid glucose study

BackgroundSeveral studies have shown significant associations between manganese superoxide dismutase (MnSOD) Val16Ala polymorphism and diabetic complications, but this association has not been explored in relation with chronic kidney disease (CKD) in Type 2 diabetes mellitus (T2DM) patients. Total antioxidant capacity (TAC) level changes in diabetic condition and may play important role in onset or progression of the disease and its complications. The present study investigated the association of MnSOD Val16Ala polymorphism and serum TAC with the risk of CKD in T2DM patients.MethodsThis nested case-control study included 280 type 2 diabetic patients with CKD and 280 age, sex and diabetes duration-matched control subjects selected from the participants of the Tehran Lipid and Glucose Study. MnSOD val16Ala (rs4880) SNP was genotyped by the Tetra-Primer ARMS-polymerase chain reaction analysis. Serum TAC was measured using ferric-reducing antioxidant power assay. Statistical analysis was performed using STATA statistical package v.12.0 or SPSS (Version 22.0).ResultsThe Ala allele of the MnSOD Val16Ala polymorphism was associated with a lower risk of CKD (odds ratio (OR), 0.55; 95% confidence interval (CI), 0.36–0.84; P = 0.006). Median serum TAC in CKD group was 920 μmol/L and was significantly lower (p < 0.001) compared to the control group (1045 μmol/L). Using an adjusted conditional logistic regression, we didn’t observe any significant interaction between MnSOD Val16Ala SNP with quartiles of serum TAC in relation to CKD.ConclusionA significant association was found between the MnSOD Val16Ala polymorphism and CKD, but this association is not affected by serum TAC level in T2DM patients.

Association of manganese superoxide dismutase Ala16Val polymorphism in the incidence of acute myocardial infarction in the Egyptians.

Background: Oxidative stress has been implicated in various diseases including atherosclerosis; the most common pathologic process underlying acute myocardial infarction (AMI). The manganese superoxide dismutase (MnSOD) antioxidant enzyme affords the major defense against reactive oxygen species (ROS) within the mitochondria. MnSOD Alanine16Valine (A16V) single nucleotide polymorphism (SNP) has been shown to decrease MnSOD detoxification activity. Aim: A case-control study was conducted to investigate the association between MnSOD A16V polymorphism and the incidence of AMI in the Egyptians, investigate the contribution of oxidative stress represented by hexanoyl lysine adduct (HEL), an oxidative stress biomarker, in the pathogenesis of AMI and finally correlate the MnSOD genotypes with HEL serum levels. Methods: A total of 200 Egyptian subjects were recruited for the study; 100 AMI patients and 100 control subjects. Genotypes of the MnSOD A16V polymorphism were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum HEL was measured by ELISA. Results: A significant difference in the distribution of the MnSOD A16V genotypes was observed; VV genotype was significantly higher in AMI than controls (p ≤ 0.0001). Also, studying the allele frequencies revealed that Val allele was significantly higher in AMI than controls (p ≤ 0.0001). Serum analysis showed higher levels of HEL in AMI patients (p = 0.0142). Furthermore, HEL levels were found to be significantly higher in VV genotype in AMI (p = 0.0273). Conclusions: Our study suggests that MnSOD A16V polymorphism is associated with increased risk of developing AMI in the Egyptians. Moreover, the VV genotype is associated with higher HEL levels.

Polymorphism of MnSOD (Val16Ala) gene in pregnancies with blighted ovum: A case-control study

Blighted ovum is one of the most common reasons for abortion during the first three months of pregnancy. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme in the human immune system. The gene is located on 6q25 chromosome and acts on mitochondrial matrix. In the case of mutation or inactivity of this enzyme, mitochondrial and nuclear DNA will severely be destructed. The most common polymorphism of its gene is Val16Ala. The aim was to investigate a possible mutation in pregnant women who had abortion during the first trimester of pregnancy due to blighted ovum. In this case-control study, 34 women were entered as the case and control groups, respectively. Genome DNA was extracted from saliva samples and its genotype was determined using Tetra-primer amplification refractory mutation system polymerase chain reaction technique. In the case group, 16 (48%) cases had Val/Val genotype, 17 (50%) were heterozygote and had Val/Ala genotype, and 1 (2%) had Ala/Ala genotype. Among controls, 7 (22%) items had Val/Val genotype, 6 (17%) had Val/Ala genotype, and 21 (61%) had Ala/Ala genotype. The frequency of TT, CT, and CC genotypes was 48%, 50%, and 2% in case group and 22%, 17%, and 61% in control group, respectively. Statistical analysis revealed a significant relationship between Val16Ala polymorphism of MnSOD gene and blighted ovum (p= 0.0003). It has concluded that a significant relationship exists between Val16Ala polymorphism of MnSOD gene and blighted ovum.

MnSOD Val16Ala polymorphism associated with retinopathy risk in diabetes: a PRISMA-compliant Meta-analysis of case-control studies.

To investigate the association of Manganese superoxide dismutase (MnSOD) Val16Ala polymorphism with diabetic retinopathy (DR). PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Subgroup, sensitivity, and cumulative analyses were performed. Publication bias was also analyzed. Eight studies were included in the pooled analysis. The MnSOD Val16Ala polymorphism was associated with the risk of DR under the dominant model (OR=0.66, 95%CI=0.48-0.91, P<0.0001), this result was demonstrated to be relatively stable in cumulative analysis. No significant publication bias was found. This polymorphism was also associated with the risk of DR in Caucasians under the dominant model (OR=0.64, 95%CI=0.42-0.97, P=0.04,) and in Asians under the recessive model (OR=0.31, 95%CI=0.11-0.88, P=0.03). These findings suggest that the MnSOD Val16Ala polymorphism is a risk factor for DR, and that more attention should be paid to carriers of these susceptibility genes.

Association between manganese superoxide dismutase (MnSOD) polymorphism and prostate cancer susceptibility: a meta-analysis.

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. 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. 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. This meta-analysis indicated that the Ala allele of the MnSOD gene polymorphism increases prostate cancer susceptibility.

Susceptibility of Patients with Manganese Superoxide Dismutase Ala16val Genetic Polymorphism to Type 2 Diabetes Mellitus and its Complications in a Sample of Lebanese Population

Oxidative stress has been frequently associated with the development of type 2 diabetes mellitus. Manganese superoxide dismutase (MnSOD) is one of the most important enzymes responsible for the defense against oxidative damage in the mitochondria. A polymorphism in the second exon of the MnSOD at position 16 that changes Ala into Val, induces changes in the structural conformation and mitochondrial transport of MnSOD. This polymorphism affects the scavenger activity of the enzyme and generates high reactive oxygen species which could exacerbate the development of type 2 diabetes and/or its complications. Relationship between MnSOD polymorphism and Type 2 diabetes mellitus and its complications remains uncertain.

U-Shaped Association between Plasma Manganese Levels and Type 2 Diabetes.

Background:Manganese is both an essential element and a known toxicant, and it plays important roles in many mechanisms in relation to type 2 diabetes (T2D). However, epidemiological studies of this relationship are rare.Objective:We investigated the association between plasma manganese and newly diagnosed T2D as well as whether the association could be modified by manganese superoxide dismutase (MnSOD) polymorphisms.Methods:We conducted a case–control study of 3,228 participants in China: 1,614 T2D patients and 1,614 controls. Concentrations of plasma magnesium were measured, and all participants were genotyped for the MnSOD Val16Ala polymorphism (rs4880).Results:A U-shaped association was observed between plasma manganese and T2D, with increased odds ratios (ORs) in relation to either low or high plasma manganese levels. Compared with the middle tertile, the multivariate-adjusted ORs [95% confidence intervals (CIs)] of T2D associated with the lowest tertile and the highest tertile of plasma manganese were 1.89 (1.53, 2.33) and 1.56 (1.23, 1.97), respectively. In spline analysis, the U-shaped association was consistently indicated, with the lowest odds of T2D at the plasma manganese concentration of 4.95 μg/L. Minor allele frequencies (C allele) of the MnSOD Val16Ala polymorphism (rs4880) in the normal glucose tolerance (NGT) and the T2D groups were 13.57% and 14.50%, respectively. The MnSOD rs4880 polymorphism was not associated with T2D, and no interaction was found between plasma manganese and the MnSOD rs4880 polymorphism in relation to T2D.Conclusions:Our results suggested a U-shaped association between plasma manganese and T2D; both low and high levels of plasma manganese were associated with higher odds of newly diagnosed T2D. The U-shaped association was not modified by the MnSOD rs4880 polymorphism.Citation:Shan Z, Chen S, Sun T, Luo C, Guo Y, Yu X, Yang W, Hu FB, Liu L. 2016. U-shaped association between plasma manganese levels and type 2 diabetes. Environ Health Perspect 124:1876–1881; http://dx.doi.org/10.1289/EHP176

Investigation of the preventative roles of manganese superoxide dismutase Ala16Val gene polymorphism in coronary artery events

Amac: Arastirmamizin amaci, mangan superoksit dismutaz (MnSOD) genine ait Ala16Val polimorfizminin koroner arter hastaligi (KAH) olan kisilerdeki genotip sikliklarini belirlemek ve genotip-kalp damar hastaligi ve genotip-biyokimyasal parametreler ve serum MnSOD aktivitesi ile etkilesimin degerlendirilmesidir. Gerec ve yontemler: MnSOD geni Ala16Val genotipleri kantitatif polimeraz zincir reaksiyonu yontemi ile saptandi. Serum MnSOD aktivitesi ELISA yontemi ile belirlendi. Bulgular: MnSOD geni Ala16Val polimorfizmi icin genotip sikliklari KAH grubunda C/C (Homozigot yabanil tip), C/T (Heterozigot), T/T (Homozigot polimorfik tip) genotipler icin sirasiyla %20.9, %41.9, %37.2 ve KAH olmayan grupta %15.5, %51.7, %32.8 olarak tespit edildi. Tum calisma grubundaki mitokondriyal MnSOD aktiviteleri, MnSOD geni Ala16Val genotiplerine gore karsilastirildiginda CC genotip tasiyicilarinin en yuksek, TT genotip tasiyicilarinin en dusuk MnSOD aktivitesine sahip oldugu belirlendi. Koroner arter hastaligi bulunmayan hastalarda MnSOD Ala16Val polimorfizminin yagsiz vucut kutlesi (p=0.01) ve yag kutlesi (p=0.05) uzerine anlamli etkileri oldugu saptandi. Ala16Val polimorfizminin heterozigot genotipe sahip KAH hastalarinda yagdan zengin gidalarla beslenme aliskanliklari diger genotiplere kiyasla daha dusuk iken, homozigot polimorfik genotipe sahip KAH hastalarinin diger genotiplere kiyasla proteinden fakir beslenme aliskanliklarini benimsedikleri goruldu. Sonuc: Tum calisma grubu degerlendirildiginde, MnSOD Ala16Val genotipleri ile beslenme aliskanliklari arasinda anlamli bir iliski bulunurken yagsiz vucut kutlesi uzerinde etkili bulunmamistir.

Association of the manganese superoxide dismutase gene Ala-9Val polymorphism with age of smoking initiation in male schizophrenia smokers.

Schizophrenia patients exhibit higher smoking rates than the general population. A growing body of evidence suggests that cigarette smoke impairs the antioxidant defense mechanisms, leading to oxidative damage. Manganese superoxide dismutase (MnSOD) is the major antioxidant in the mitochondria, catalyzing the metabolism of superoxide radicals to form hydrogen peroxide. Since the identification of a well-characterized functional polymorphism, Ala-9Val of MnSOD, a number of studies have evaluated the association between Val-9Ala and schizophrenia or cancer. In this study, we hypothesized that the functional polymorphism of MnSOD Ala-9Val was associated with smoking in patients with schizophrenia. This polymorphism was genotyped in 666 chronic male schizophrenia patients (smoker/never-smoker = 507/159) and 660 male controls (smoker/never-smoker = 360/300) using a case-control design. The cigarettes smoked per day (CPD) and smoking behaviors were evaluated by clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND). The results showed no significant differences in MnSOD Ala-9Val genotype and allele distributions between the patients and healthy controls or between smokers and never-smokers in either patients or healthy controls alone. The smokers with the Ala allele started smoking significantly earlier (19.9 ± 5.8 vs. 21.7 ± 6.5 years, P = 0.005) only in patients. These results suggest that the MnSOD Ala-9Val polymorphism may not influence smoking status in a Chinese male schizophrenia population, but may influence the age at which smoking is started among schizophrenia smokers.

A pilot study of the association of manganese superoxide dismutase and glutathione peroxidase 1 single gene polymorphisms with prostate cancer and serum prostate specific antigen levels.

IntroductionThe aim of the study was to evaluate the potential association of single gene polymorphisms of the antioxidant enzymes manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX1) with prostate cancer (PCa).Material and methodsManganese superoxide dismutase and glutathione peroxidase 1 genotypes and allele frequencies in 49 prostate cancer cases (PCa group) and 98 control subjects were determined. Analysis of genotypes in control group individuals were performed in two subgroups according to serum prostate-specific antigen levels: the control group (n = 49), with prostate specific antigen (PSA) level < 4 ng/ml; and the nonPCa-high PSA control group (n = 49), with serum PSA > 4 ng/ml. Determination of MnSOD Ala-9Val and GPX1 Pro198Leu polymorphisms was performed using real-time polymerase chain reaction amplification.ResultsNo association was found between GPX1 polymorphisms and PCa in all groups (p > 0.05). In the PCa group, the frequency of homozygote Val allele carriers was significantly higher in comparison to nonPCa-high PSA control cases. Therefore, Val/Val genotype was found significantly suspicious for PCa risk (OR = 2.48; 95% CI: 1.37–4.48; p = 0.002). Furthermore, an overall protective effect of the Ala allele of the MnSOD polymorphism on PCa risk was detected. These findings in this small Turkish population suggested that individual risk of PCa may be modulated by MnSOD polymorphism especially in patients with high PSA, but GPX1 polymorphism seemed to have no effect on PCa risk.ConclusionsThe presence of genetic variants of antioxidant enzymes could have a potential influence on genesis of prostatic malignancy.

Meta-Analyses of Manganese Superoxide Dismutase Activity, Gene Ala-9Val Polymorphism, and the Risk of Schizophrenia.

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.

Association of the Ala16Val MnSOD gene polymorphism with plasma leptin levels and oxidative stress biomarkers in obese patients

Chronic oxidative stress is a major characteristic of obesity. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme known to be present within mitochondria and is considered a main defense against oxidative stress. The aim of this study was to investigate the association between the MnSOD gene Ala16Val polymorphism in obesity in terms of body mass index (BMI), lipid parameters, plasma leptin levels, homeostasis model assessment of insulin resistance (HOMA-IR), and oxidative stress biomarkers. The study included 150 obese and 120 non-obese subjects. The MnSOD Ala16Val polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma leptin levels, serum lipid, superoxide dismutase (SOD), malondialdehyde (MDA), and anthropometric parameters were measured. No association was found between the MnSOD gene Ala16Val polymorphism and BMI in the study or control group. Strikingly, in the study group, obese subjects with the VV genotype had significantly higher plasma leptin levels (p<0.001) than those with the AA and AV genotypes. Serum total cholesterol (p<0.01) and MDA (p<0.001) levels were significantly higher in subjects with the VV genotype for MnSOD in the obese and non-obese groups. In the obese group, subjects with the VV genotype had significantly lower SOD (p<0.001) activity than the AA and AV genotypes. Our results suggest that the MnSOD gene polymorphism was associated with leptin levels and superoxide dismutase activity in the obese group but had no direct association with obesity. Moreover, the Ala16Val polymorphism has a significant effect on lipid profiles and MDA levels in both obese and non-obese subjects.