Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis: Polish population study and a meta-analysis

Żur-Wyrozumska, Kamila; Pera, Joanna; Dziubek, Anna; Sado, Małgorzata; Golenia, Aleksandra; Słowik, Agnieszka; Dziedzic, Tomasz

doi:10.1016/j.pjnns.2017.01.008

Cited by 7 publications

(6 citation statements)

References 26 publications

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“…The basic features of the 25 case-control studies ( Nakata et al, 1998 ; Zheng et al, 2000 ; Yingdong et al, 2002 ; Li et al, 2003 ; Zhang et al, 2004 ; Yan et al, 2004 ; Fang and Wu, 2004 ; Ye et al, 2004 ; Żur-Wyrozumska et al, 2017 ; Fang et al, 2005 ; Dikmen et al, 2006 ; Sazci et al, 2006 ; Hu et al, 2007 ; Shen et al, 2007 ; Zhang et al, 2008 ; Ruigrok et al, 2010 ; Hultdin et al, 2011 ; Somarajan et al, 2011 ; Atadzhanov et al, 2013 ; Rui-Rui et al, 2013 ; Das et al, 2015 ; Shao et al, 2016 ; Hu et al, 2016 ; Abidi et al, 2018 ; Jiang et al, 2018 ) included are shown in Table 1 . The incorporated studies ranged from 1998 to 2018, involving mainly Asian populations and some European and African communities.…”

Section: Resultsmentioning

confidence: 99%

“…The incorporated studies ranged from 1998 to 2018, involving mainly Asian populations and some European and African communities. Three different races were involved in these 25 selected studies: two ( Atadzhanov et al, 2013 ; Abidi et al, 2018 ) African, three ( Dikmen et al, 2006 ; Sazci et al, 2006 ; Hultdin et al, 2011 ) Caucasian and the remaining 17 ( Nakata et al, 1998 ; Zheng et al, 2000 ; Yingdong et al, 2002 ; Zhang et al, 2004 ; Yan et al, 2004 ; Fang and Wu, 2004 ; Ye et al, 2004 ; Żur-Wyrozumska et al, 2017 ; Hu et al, 2007 ; Zhang et al, 2008 ; Rui-Rui et al, 2013 ; Shao et al, 2016 ; Hu et al, 2016 ; Jiang et al, 2018 ) Asian. The control population in three of the 25 studies ( Li et al, 2003 ; Shen et al, 2007 ; Das et al, 2015 ) did not meet Hardy-Weinberg equilibrium and be excluded.…”

Section: Resultsmentioning

confidence: 99%

“…(Nakata et al, 1998;Zheng et al, 2000;Yingdong et al, 2002;Zhang et al, 2004;Yan et al, 2004;Fang and Wu, 2004;Ye et al, 2004;Żur-Wyrozumska et al, 2017;Hu et al, 2007;Zhang et al, 2008;Rui-Rui et al, 2013;Shao et al, 2016;Hu et al, 2016;Jiang et al, 2018) Asian. The control population in three of the 25 studies(Li et al, 2003;Shen et al, 2007;Das et al, 2015) did not meet Hardy-Weinberg equilibrium and be excluded.…”

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confidence: 99%

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A systematic review and meta-analysis expounding the relationship between methylene tetrahydrofolate reductase gene polymorphism and the risk of intracerebral hemorrhage among populations

et al. 2022

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Background: The relationship between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphism with the risk of intracerebral hemorrhage (ICH) has remained to be controversial in recent years. This meta-analysis is aimed to confirm the association of these.Methods: Systematically searching the related studies from the PubMed, Embase, Cochrane Library, China national knowledge internet database from 1 January 1990 to 1 June 2022. The odd ratio (ORs) and 95% confidence interval (CIs) of gene-disease correlation in various gene models were calculated by fixed or random effect model of meta-analysis. We included 20 case-control studies in this meta-analysis with a total of 1,989 ICH patients and 4,032 health controls originated from Asian, Caucasian, and African populations.Results: The statistical analysis demonstrated the association of MTHFR C677T gene polymorphism with ICH in allele model [ORT VS. C = 1.20 (95%CI: 1.06–1.36)]; homozygote model [OR TT VS. CC = 1.50 (95%CI: 1.20–1.88)]; dominant model [OR CT+ TT VS. CC = 1.23 (95%CI: 1.03–1.48)] and recessive model [ORTT VS. CT+CC = 1.37 (95%CI: 1.17–1.60)]. Besides, we also found the relationship of MTHFR C677T gene polymorphism with Asian in four comparison model (ORT VS. C = 1.19.95%CI:1.09–1.37, ORTT VS. CC = 1.46.95%CI: 1.15–1.85, OR CT+ TT VS. CC = 1.25.95%CI: 1.01–1.54, ORTT VS. CT+CC = 1.34.95%CI: 1.54–1.17) and Caucasian in four comparison model (ORT VS. C = 1.90.95%CI: 1.22–2.97, ORTT VS. CC = 2.67.95%CI: 1.42–5.00, OR CT+ TT VS. CC = 1.56.95%CI: 1.05–2.32, ORTT VS. CT+CC = 2.25.95%CI: 1.46–4.00). But no statistically significant correlation between A1298C polymorphism and the occurrence of ICH was detected in four studies.Conclusion: MTHFR C677T gene polymorphism increases the risk of ICH in Asian and Caucasian populations but has no impact on the incidence in African communities. More importantly, the risk of ICH increases in TT genotype individuals in comparison to CT and CC genotype individuals in Asian and Caucasian populations.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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A systematic review and meta-analysis expounding the relationship between methylene tetrahydrofolate reductase gene polymorphism and the risk of intracerebral hemorrhage among populations

et al. 2022

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“…However, a study performed in an Italian population failed to show an association between the C677T polymorphism and the risk of ALS [105]. A recent meta-analysis suggested that the TT polymorphism could be a genetic risk for sporadic ALS in the Caucasian population [106]. If the association between hyperhomocysteinemia and ALS is proven to be causal, then reducing the levels of Hcy could potentially reduce the incidence of ALS.…”

Section: Abnormal Metabolism Of Saas In Alsmentioning

confidence: 99%

Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS

Lee,

Henderson,

Aylward

et al. 2024

IJMS

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Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have a range of functions and could influence ALS by several mechanisms. Here, we review the possible role of gut-derived neurotoxins/excitotoxins. We review the evidence of gut symptoms and gut dysbiosis in ALS. We then examine a possible role for gut-derived toxins by reviewing the evidence that these molecules are toxic to the central nervous system, evidence of their association with ALS, the existence of biochemical pathways by which these molecules could be produced by the gut microbiota and existence of mechanisms of transport from the gut to the blood and brain. We then present evidence that there are increased levels of these toxins in the blood of some ALS patients. We review the effects of therapies that attempt to alter the gut microbiota or ameliorate the biochemical effects of gut toxins. It is possible that gut dysbiosis contributes to elevated levels of toxins and that these could potentially contribute to ALS pathogenesis, but more work is required.

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“…Variation in genes involved in the folate pathway has been suggested as a possible factor implicated in ALS since this vitamin is essential to DNA synthesis and homocysteine (Hcy) metabolism, the dysregulation folate metabolism unbalances the cellular homeostasis, and could contribute to neurodegenerative processes in motor neurons [16,17]. The Methylenetetrahydrofolate reductase (MTHFR) gene stands out as a potential target, considering that it is responsible for encoding the MTHFR enzyme, which plays a crucial role in intracellular folate metabolism [18].…”

Section: Introductionmentioning

confidence: 99%

Do MTHFR C677T Genetic Polymorphism Influence in the Pathogenesis of Amyotrophic Lateral Sclerosis?

Azevedo

Santos

Oliveira

et al. 2021

Preprint

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Amyotrophic Lateral Sclerosis (ALS) is a progressive and lethal neurodegenerative disease without a definitive diagnostic test and effective treatment. A plethora of studies suggest that genetic factors play an important role in ALS development, and potentially link folate pathway dysregulation to disease pathogenesis. This study aims to evaluate folate dysregulation due to MTHFR C677T polymorphism and other factors such as sociodemographic and clinical, to better elucidate the involvement of these factors in ALS pathogenesis, and to investigate possible biomarkers for use as disease diagnostics or prognostics. This hospital-based case-control study analyzed 101 patients diagnosed with ALS and 119 considered healthy, with no suspicion or diagnosis of neurodegenerative disease. Blood samples were collected, stored, and underwent DNA extraction. Clinical and sociodemographic data from patients were collected through a questionnaire, as well as consultation of medical records. Genotypic analyses were performed using PCR-RFLP, and statistical analysis of clinical and genotypic data was conducted with SPSS software, version 23. The results show a higher presence of the mutant genotype (p = 0.02) in the case group, and suggest that mutant allele (T) is a risk factor for ALS susceptibility (OR = 1.54; 95% CI = 1.05–2.29; p = 0.03). Mutant genotype (T/T) interacts with both demographics (White p = 0.005 / Brown p = 0,001) and clinical factors (Physical activity p = 0.006) as risk factors for ALS. Also, a significant difference in alcohol consumption (p = 0.001) between the case and control group was observed. Moreover, a statistical trend towards faster disease progression and death was observed for patients with the mutant allele (T) (p = 0.06). Thus, the results of this study suggest that folate deficiency due to MTHFR C677T polymorphism is implicated in ALS through pathogenic mechanisms and interaction with other risk factors, resulting in faster disease progression and early death.

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Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis: Polish population study and a meta-analysis

Abstract: Although we did not find the association between C677T polymorphism of MTHRF gene and risk of ALS in Polish population, the results of meta-analysis suggest that the TT genotype can be a genetic risk factor for ALS in Caucasian population.

Cited by 7 publications

References 26 publications

A systematic review and meta-analysis expounding the relationship between methylene tetrahydrofolate reductase gene polymorphism and the risk of intracerebral hemorrhage among populations

A systematic review and meta-analysis expounding the relationship between methylene tetrahydrofolate reductase gene polymorphism and the risk of intracerebral hemorrhage among populations

Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS

Do MTHFR C677T Genetic Polymorphism Influence in the Pathogenesis of Amyotrophic Lateral Sclerosis?

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