Association of MTHFR, MTR, and MTRR polymorphisms with Parkinson's disease among ethnic Chinese in Taiwan

Fong, Chin-Shih; Shyu, Hann-Yeh; Shieh, Jia‐Ching; Fu, Yi-Ping; Chin, Ting‐Yu; Wang, Hsiao-Wei; Cheng, Chun-Wen

doi:10.1016/j.cca.2010.11.004

Cited by 37 publications

(29 citation statements)

References 44 publications

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“…Studies on MTRR A66G polymorphism in association with PD are sparse. Fong et al observed positive association of MTRR A1049G with PD risk in Taiwanese population [24]. Carriers of MTRR 66G-allele were reported to have 6.6 % higher homocysteine levels compared to 66AA genotype when riboflavin is marginally deficient or optimal [25].…”

Section: Discussionmentioning

confidence: 97%

Comparative analysis of four disease prediction models of Parkinson’s disease

et al. 2015

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Parkinson's disease (PD) is a multi-factorial disorder with high-penetrant mutations accounting for small percentage of PD. Our previous studies demonstrated individual association of genetic variants in folate, xenobiotic, and dopamine metabolic pathways with PD risk. The rational of the study was to develop a risk prediction model for PD using these genetic polymorphisms along with synuclein (SNCA) polymorphism. We have generated additive, multifactor dimensionality reduction (MDR), recursive partitioning (RP), and artificial neural network (ANN) models using 21 SNPs as inputs and disease outcome as output. The clinical utility of all these models was assessed by plotting receiver operating characteristics curves where in area under the curve (AUC) was used as an index of diagnostic utility of the model. The additive model was the simplest and exhibited an AUC of 0.72. The MDR model showed significant gene-gene interactions between SNCA, DRD4VNTR, and DRD2A polymorphisms. The RP model showed SHMT C1420T as important determinant of PD risk. This variant allele was found to be protective and this protection was nullified by MTRR A66G. Inheritance of SHMT wild allele and SNCA intronic polymorphism was shown to increase the risk of PD. The ANN model showed higher diagnostic utility (AUC = 0.86) compared to all the models and was able to explain 56.6% cases of sporadic PD. To conclude, the ANN model developed using SNPs in folate, xenobiotic, and dopamine pathways along with SNCA has higher clinical utility in predicting PD risk compared to other models.

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Section: Discussionmentioning

confidence: 97%

Comparative analysis of four disease prediction models of Parkinson’s disease

et al. 2015

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“…But for MTR A2756G and MTRR A66G polymorphisms, there are not enough studies. Hence, further studies are need to be conducted (Table 1) [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58]. …”

Section: Genetic Susceptibility and The Risk Of Msmentioning

confidence: 99%

The Role of Folate Dependent Genetic Susceptibility in The Risk of Multiple Sclerosis

Asci¹,

Karahalıl²

2017

J Neurol Neurosci

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Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) of unknown cause. Epidemiological studies implicate that genetic and environmental factors interplay major roles in the etiology of MS. Several investigators have reported elevated plasma homocysteine and reduced folate and B vitamin levels in MS. Aberrations in one-carbon metabolism have impact in the pathophysiology by genetic susceptibility and increased the risk of MS. Furthermore, abnormalities in a carbon metabolism pathway may result from environmental factors such as reduced levels of vitamin B and folate due to inadequate B vitamin and folate intake from foods or the problems on their synthesis, and genetic factors such as polymorphism in folate -dependent enzymes.

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“…However, these reports as well as literature review [26, 85, 90, 91], revealed that the most pronounced increases of tHcy were noted in AD and PD patients with the C677T MTHFR TT genotype, particularly for patients with low plasma folate levels. Moreover, in PD and AD patients bearing the MTHFR CT genotype, the process of Hcy to Cys transsulfuration was disturbed, resulting in higher Cys levels [8].…”

Section: Polymorphisms Of Mthfr Mtr Mthfd1 and The Level Of Biothiomentioning

confidence: 99%

“…On the other hand, the heterozygous AC genotype of the A1298C polymorphism has been observed in PD patients more frequently at various stages of the disease, and the most pronounced disturbances in Hcy remethylation and transsulfuration have been manifested in MTHFR 1298AC genotype carriers [8]. Nevertheless, synergistic effects in the folate metabolic pathway of MTHFR and other gene polymorphisms in the pathogenesis of PD probably exist [90]. …”

Section: Polymorphisms Of Mthfr Mtr Mthfd1 and The Level Of Biothiomentioning

confidence: 99%

Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment

Różycka

Jagodzińśki

Kozubski

et al. 2014

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An elevated concentration of total homocysteine (tHcy) in plasma and cerebrospinal fluid is considered to be a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). Homocysteine (Hcy) levels are influenced by folate concentrations and numerous genetic factors through the folate cycle, however, their role in the pathogenesis of PD remains controversial. Hcy exerts a neurotoxic action and may participate in the mechanisms of neurodegeneration, such as excitotoxicity, oxidative stress, calcium accumulation, and apoptosis. Elevated Hcy levels can lead to prooxidative activity, most probably through direct interaction with N-methyl-D-aspartate (NMDA) receptors and sensitization of dopaminergic neurons to age-related dysfunction and death. Several studies have shown that higher concentration of Hcy in PD is related to long-term administration of levodopa (L-dopa). An elevation of plasma tHcy levels can also reflect deficiencies of cofactors in remethylation of Hcy to methionine (Met) (folates and vitamin B12) and in its transsulfuration to cysteine (Cys) (vitamin B6). It is believed that the increase in the concentration of Hcy in PD can affect genetic polymorphisms of the folate metabolic pathway genes, such as MTHFR (C677T, A1298C and G1793A), MTR (A2756G), and MTHFD1 (G1958A), whose frequencies tend to increase in PD patients, as well as the reduced concentration of B vitamins. In PD, increased levels of Hcy may lead to dementia, depression and progression of the disease.

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Association of MTHFR, MTR, and MTRR polymorphisms with Parkinson's disease among ethnic Chinese in Taiwan

Cited by 37 publications

References 44 publications

Comparative analysis of four disease prediction models of Parkinson’s disease

Comparative analysis of four disease prediction models of Parkinson’s disease

The Role of Folate Dependent Genetic Susceptibility in The Risk of Multiple Sclerosis

Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment

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