scholarly journals Glutathione S-transferase Omega 2 DD genotype is associated with an increased risk of sporadic amyotrophic lateral sclerosis in Chinese men

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110332
Author(s):  
Zhiliang Fan ◽  
Hong Jiang ◽  
Xueqin Song ◽  
Yansu Guo ◽  
Xinying Tian
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Healthy Subjects ◽  
Chinese Population ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Glutathione S Transferase ◽  
Genotype Frequencies ◽  
Sporadic Als ◽  
Increased Risk ◽  
Chi Squared ◽  
Lateral Sclerosis

Objective To investigate whether GSTA1, GSTO2, and GSTZ1 are relevant to an increased risk of amyotrophic lateral sclerosis (ALS) in a Chinese population. Methods In this study, 143 sporadic ALS (sALS) patients (83 men, 60 women) and 210 age- and sex-matched healthy subjects were enrolled. Blood samples were collected by venipuncture. Genomic DNA was isolated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) according to the manufacturer’s instructions. The potential associations between ALS and GSTA1, GSTO2, and GSTZ1 polymorphisms were estimated using chi-squared analysis and unconditional logistic regression. Results The D allele and genotype frequencies of GSTO2 were increased in sALS patients compared with healthy subjects, indicating that the GSTO2 DD genotype was associated with an increased risk of sALS (odds ratio [OR] = 3.294, 95% confidence interval [CI] = 1.039–10.448). However, a significant association between the DD genotype and the risk of sALS was evident in men only (OR = 7.167, 95% CI = 1.381–37.202). Conclusion This study revealed that the D allele and genotype frequencies of GSTO2 were increased in sALS patients. The GSTO2 DD genotype was associated with an increased risk of sALS in men in a Chinese population.

scholarly journals Evidence for polygenic and oligogenic basis of Australian sporadic amyotrophic lateral sclerosis

2020 ◽  
pp. jmedgenet-2020-106866 ◽  
Author(s):  
Emily P McCann ◽  
Lyndal Henden ◽  
Jennifer A Fifita ◽  
Katharine Y Zhang ◽  
Natalie Grima ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Genetic Variation ◽  
Genetic Analysis ◽  
Genetic Variants ◽  
Age Of Onset ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Whole Genome ◽  
Identity By Descent ◽  
Sporadic Als ◽  
Lateral Sclerosis

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with phenotypic and genetic heterogeneity. Approximately 10% of cases are familial, while remaining cases are classified as sporadic. To date, >30 genes and several hundred genetic variants have been implicated in ALS.MethodsSeven hundred and fifty-seven sporadic ALS cases were recruited from Australian neurology clinics. Detailed clinical data and whole genome sequencing (WGS) data were available from 567 and 616 cases, respectively, of which 426 cases had both datasets available. As part of a comprehensive genetic analysis, 853 genetic variants previously reported as ALS-linked mutations or disease-associated alleles were interrogated in sporadic ALS WGS data. Statistical analyses were performed to identify correlation between clinical variables, and between phenotype and the number of ALS-implicated variants carried by an individual. Relatedness between individuals carrying identical variants was assessed using identity-by-descent analysis.ResultsForty-three ALS-implicated variants from 18 genes, including C9orf72, ATXN2, TARDBP, SOD1, SQSTM1 and SETX, were identified in Australian sporadic ALS cases. One-third of cases carried at least one variant and 6.82% carried two or more variants, implicating a potential oligogenic or polygenic basis of ALS. Relatedness was detected between two sporadic ALS cases carrying a SOD1 p.I114T mutation, and among three cases carrying a SQSTM1 p.K238E mutation. Oligogenic/polygenic sporadic ALS cases showed earlier age of onset than those with no reported variant.ConclusionWe confirm phenotypic associations among ALS cases, and highlight the contribution of genetic variation to all forms of ALS.

scholarly journals The rs2619566, rs10260404, and rs79609816 Polymorphisms Are Associated With Sporadic Amyotrophic Lateral Sclerosis in Individuals of Han Ancestry From Mainland China

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Zhang ◽  
Weiwen Qiu ◽  
Fan Hu ◽  
Xiong Zhang ◽  
Youqing Deng ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Genome Wide Association Study ◽  
Mainland China ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Inositol Polyphosphate ◽  
A Genome ◽  
Increased Risk ◽  
Independent Case ◽  
Candidate Loci ◽  
Lateral Sclerosis

The pathogenesis of sporadic amyotrophic lateral sclerosis (sALS) remains unknown; however, recent research suggests that genetic factors may play an important role. This study aimed at investigating possible genetic risk factors for the pathogenesis of sALS. In our previous study, we conducted a genome-wide association study (GWAS) in 250 sALS patients and 250 control participants of Han ancestry from mainland China (HACM) and retrospectively analyzed the previously reported candidate loci related with sALS including our GWAS investigated results. In this study, twenty-seven candidate loci that were most likely associated with sALS were selected for further analysis in an independent case/control population of 239 sALS patients and 261 control subjects of HACM ethnicity using sequenom massARRAY methodology and DNA sequencing. We discovered that the polymorphism rs2619566 located within the contactin-4 (CNTN4) gene, rs10260404 in the dipeptidyl-peptidase 6 (DPP6) gene, and rs79609816 in the inositol polyphosphate-5-phosphatase B (INPP5B) gene were strongly associated with sALS in subjects of HACM ethnicity. Subjects harboring the minor C allele of rs2619566 and the minor T allele of rs79609816 exhibited an increased risk for sALS development, while carriers of the minor C allele of rs10260404 showed a decreased risk of sALS development compared to the subjects of other genotypes. The polymorphisms of rs2619566, rs10260404, and rs79609816 may change or affect the splicing, transcription, and translation of CNTN4, DPP6, and INPP5B genes and may play roles in the pathogenesis of sALS roles in the pathogenesis of sALS.

scholarly journals SMN1 copy number as a modifying factor of survival in Serbian patients with sporadic amyotrophic lateral sclerosis

2018 ◽  
Vol 146 (11-12) ◽  
pp. 646-652
Author(s):  
Milos Brkusanin ◽  
Irena Jeftovic-Velkova ◽  
Vladimir Jovanovic ◽  
Stojan Peric ◽  
Jovan Pesovic ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Copy Number ◽  
Rating Scale ◽  
Cox Regression ◽  
Diagnostic Delay ◽  
Susceptibility Genes ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Cox Regression Analysis ◽  
Sporadic Als ◽  
Lateral Sclerosis

Introduction/Objective. Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The majority of cases are apparently sporadic ALS (SALS) with variants in susceptibility genes or sometimes in high-risk ALS genes. Two ALS susceptibility genes are SMN1, whose functional loss causes spinal muscular atrophy (SMA), and a nearly identical SMN2 gene, which modulates SMA severity. In this study we examined the association of copy number variations (CNVs) of SMN1 and SMN2 genes and two additional genes, SERF1 and NAIP, residing in the same genomic region (i.e. 5q13.2 segmental duplication), with SALS in patients from Serbia. Methods. Multiplex ligation-dependent probe amplification was used to determine CNVs of each gene in a clinically well-characterised group of 153 Serbian SALS patients and 153 controls. Results. Individual association between SMN1, SMN2, SERF1 or NAIP CNVs and SALS susceptibility or survival was not found. Survival curves based on the multivariable Cox regression analysis showed that three SMN1 copies, lower ALS Functional Rating Scale Revised (ALSFRS-R) score at the time of diagnosis, faster decline of the ALSFRS-R score over time, and shorter diagnostic delay result in shorter survival of Serbian SALS patients. Conclusion. Clinical variables might be complemented with the SMN1 copy number to improve prediction of survival in Serbian SALS patients.

scholarly journals Glutathione S-Transferase Rescues Motor Neuronal Toxicity in Fly Model of Amyotrophic Lateral Sclerosis

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 615
Author(s):  
Sun Joo Cha ◽  
Yeo Jeong Han ◽  
Hyun-Jun Choi ◽  
Hyung-Jun Kim ◽  
Kiyoung Kim
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neuromuscular Junctions ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Oxygen Species ◽  
Glutathione S Transferase ◽  
Neuronal Toxicity ◽  
Drosophila Model ◽  
Locomotive Activity ◽  
Underlying Mechanisms ◽  
Lateral Sclerosis

Transactive response DNA-binding protein-43 (TDP-43) is involved in the pathology of familial and sporadic amyotrophic lateral sclerosis (ALS). TDP-43-mediated ALS models in mice, Drosophila melanogaster, and zebrafish exhibit dysfunction of locomotor function, defective neuromuscular junctions, and motor neuron defects. There is currently no effective cure for ALS, and the underlying mechanisms of TDP-43 in ALS remain poorly understood. In this study, a genetic screen was performed to identify modifiers of human TDP-43 (hTDP-43) in a Drosophila model, and glutathione S-transferase omega 2 (GstO2) was found to be involved in hTDP-43 neurotoxicity. GstO2 overexpressed on recovered defective phenotypes resulting from hTDP-43, including defective neuromuscular junction (NMJ) boutons, degenerated motor neuronal axons, and reduced larvae and adult fly locomotive activity, without modulating the levels of hTDP-43 protein expression. GstO2 modulated neurotoxicity by regulating reactive oxygen species (ROS) produced by hTDP-43 in the Drosophila model of ALS. Our results demonstrated that GstO2 was a key regulator in hTDP-43-related ALS pathogenesis and indicated its potential as a therapeutic target for ALS.

Progesterone and cortisol levels in sporadic amyotrophic lateral sclerosis (sALS): correlation with prognostic factors

2011 ◽  
Vol 6 (1) ◽  
Author(s):  
Gisella Gargiulo Monachelli ◽  
Maria Meyer ◽  
Gabriel Rodríguez ◽  
Laura Garay ◽  
Roberto E. Sica ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Prognostic Factors ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Sporadic Als ◽  
Bulbar Onset ◽  
Als Patients ◽  
Short Time ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Worse prognostic factors in ALS are: (a) advanced age, (b) bulbar onset, and (c) short time between onset and diagnosis. Progesterone (PROG) has been associated with neuroprotective and promyelinating activities in injury, ischemia and degeneration of the central and peripheral nervous system. Cortisol is connected to the response to stress situations and could contribute to neuronal damage. The goals of this study were: (i) to investigate whether PROG levels are modified by ALS prognostic factors and (ii) to determine whether cortisol follows the same pattern. We determined serum steroid levels in 27 patients with sporadic ALS (sALS) and 21 controls. Both steroid hormones showed significantly increased levels in ALS patients versus controls (mean±SEM: PROG ALS vs. control: 0.54±0.05 vs. 0.39±0.04 ng/mL, p<0.05; cortisol ALS vs. control: 17.02±1.60 vs. 11.83±1.38 μg/dL, p<0.05).

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