Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Certain mutations (TT homozygous; CT heterozygous; CC wild-type) of the methylenetetrahydrofolate (MTHFR) gene and long-term levodopa application in patients with Parkinson's disease (PD) support onset of hyperhomocysteinemia. Total plasma homocysteine (t-hcys) depends on B6, B12, folic acid, all of which support remyelination from t-hcys to methionine. Objective of this trial were to compare B6, B12, folic acid and t-hcys levels in plasma of 83 levodopa treated PD patients and 44 controls. PD patients with the CT or TT genotype had significant higher t-hcys levels than controls or PD patients with the CC allele. Concentrations of B6 or B12 did not differ, but folic acid was significant higher in PD patients with the CT mutation. We recommend MTHFR genotyping, t-hcys monitoring and early vitamin supplementation in PD patients. The folic acid increase in PD patients with the CT allele is hypothetically due to an endogenous upregulation of folic acid absorption to decrease t-hcys.
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PMID:MTHFR C677T polymorphism, folic acid and hyperhomocysteinemia in levodopa treated patients with Parkinson's disease. 1535 85

Both methylenetetrahydrofolate (MTHFR) C677T genotype and levodopa treatment may give rise to elevated serum homocysteine levels in parkinsonian patients. We aimed to clarify the interplay of these factors in pathogenesis of Parkinson's disease (PD)-related hyperhomocysteinemia. Total serum levels of homocysteine (tHcy) and MTHFR C677T genotype were investigated in levodopa-treated and -untreated parkinsonian ("de novo") patients, as well as in control healthy subjects matched by age and gender (N=83, 30 and 53, respectively). MTHFR C677T genotypes were equally distributed in PD patients and control subjects, the T allele homozygosity being observed in app. 12-17% cases. tHcy concentrations were significantly higher in both levodopa-treated and -untreated PD patients than in control subjects, and in TT homozygotes than in CT or CC genotype carriers. tHcy levels significantly correlated with the duration of the disease in PD treated patients only, reaching the maximum after 3-6 years. However, there was no correlation between tHcy levels and total daily intake of levodopa in the same group of PD patients. In conclusion, MTHFR C677T genotype is a significant factor for hyperhomocysteinemia in patients with PD, levodopa-untreated and probably even more in levodopa-treated PD patients.
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PMID:Homocysteine serum levels and MTHFR C677T genotype in patients with Parkinson's disease, with and without levodopa therapy. 1677 68

Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are accompanied by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo2dG) and alterations in levels of homocysteine (Hcy), methionine (Met), and cysteine (Cys). Hcy may undergo remethylation due to involvement of MTHFR, MTR and MTHFD1 proteins. Present studies are aimed at determination of 8-oxo2dG, Hcy, Met, and Cys in AD and PD patients as well as in control groups, using HPLC/EC/UV, as well as estimation, by restriction analysis, frequency of following gene polymorphisms: MTHFR (C677T, A1298C, G1793A), MTHFD1 (G1958A), and MTR (A2756G). In AD there were significant differences of the levels of only Cys (GG, MTHFR, G1793A) and Met/Hcy (AA, MTHFD1, G1958A) whereas in PD there were more significant differences of the levels of thiols: Hcy [MTHFR: CT (C677T) and GG (G1793A); MTR, AG (A2756G)], Met [MTR, AA (A2756G)], Cys [MTR, AG (A2756G)], and Met/Hcy [MTHFR: CC, CT (C677T) and AA (A1298C), and GG (G1793A); MTHFD1 AA(G1958A); MTR AA(A2756G)]. Significant differences in the levels of Cys/Hcy, MTHFD1 GA (G1958) were varied between AD and PD groups. The results indicate that of the enzymes studied only polymorphisms of folate-dependent enzyme MTHFD1 have pointed to significant differences in intensity of turnover of circulating thiols between AD and PD patients.
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PMID:Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer's and Parkinson's diseases. 1769 Dec 19

High plasma homocysteine levels have been observed in Parkinson's disease (PD) patients treated with levodopa. In this study, we investigated the effects of C677T and A1298C MTHFR polymorphisms, in association with L-DOPA daily dose and vitamin status, on hyperhomocysteinemia development in PD patients. Plasma homocysteine and folate/vitamin B12 levels were assayed in 49 L-DOPA-treated PD patients, and compared with those of 86 healthy subjects. Genotyping for MTHFR polymorphisms was carried out by DG-DGGE. Homocysteine levels were significantly higher in patients than in controls (16.3 +/- 5.7 vs. 11.7 +/- 2.7 micromol/l, P < 0.01). No significant differences were found between patients and controls with regard to folate/vitamin B12 levels, and MTHFR allele distribution. The TT+AA genotype was significantly more frequent in PD patients than in controls (32.5% vs. 17.4%, P < 0.05), but not associated with an increased risk for PD (OR = 2.3, CI = 1.0-5.2). Further, patients carrier of this genotype exhibited a mild hyperhomocysteinemia (22.1 +/- 4.9 micromol/l), while a protective effect was observed in patients having the CC+AA genotype (11.2 +/- 1.6 micromol/l; OR = 0.19, CI = 0.06-0.59). Interestingly, homocysteine levels were also moderately increased in patients with CT heterozygous genotype, in the context of either AA or AC (14.5 +/- 3.6 micromol/l), in comparison to subjects with the CC + AA genotype. Finally, we did not find any significant association of combined C677T and A1298C MTHFR polymorphisms with an increased risk for hyperhomocysteinemia in PD patients. A better understanding of the role of homocysteine and MTHFR genotypes in PD is needed to reveal novel approaches for disease management.
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PMID:Effect of MTHFR polymorphisms on hyperhomocysteinemia in levodopa-treated Parkinsonian patients. 1791 82

A case-control study was designed to investigate a possible genetic susceptibility of the MTHFR C677T polymorphism and assess whether the genetic polymorphism could be a predictor of levodopa-induced adverse effects in patients with Parkinson's disease (PD) of Chinese descent living in Taiwan. There were 94 sporadic PD patients with levodopa therapy at least for five years and 146 control subjects, matched by sex and gender, in this study. Results revealed that there were no differences of the allelic and genotypic frequencies of the MTHFR C677T polymorphism between PD patients and the controls. Analysis of age at onset stratified by MTHFR C677T polymorphism showed a trend of early age at onset in the PD patients carrying with T allele. The genetic influence was particularly significant in late-onset PD (onset age at or older than 60 years) with an early age at onset for 3.4 years. However, the MTHFR C677T polymorphism was not associated with the risk to develop dyskinesia, motor fluctuation and psychosis induced by levodopa in PD patients. In conclusion, results of the study revealed that the MTHFR C677T polymorphism could significantly influence age at onset of PD in Chinese population, but neither as a genetic susceptibility nor as a predictor of levodopa-induced adverse effects in PD.
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PMID:5,10-methylenetetrahydrofolate reductase C677T gene polymorphism can influence age at onset of Parkinson's disease. 1796 54

The authors present the current opinion on the significance of molecular biology in individualized therapy. Pharmacogenetics is a new branch of clinical pharmacology dealing with the influence of genetic factors on drugs with special focus on interpersonal differences to drug response. The article includes basic rules of pharmacogenetics as well as its use in clinical practice. Individualized treatment of Parkinson's disease is not widely known although interpersonal differences to drug response is clearly stated. There is some evidence that varied efficacy of treatment and risk of motor and mental complications can be of genetic origin. Some results concerning the relationship between genetic polymorphism of COMT, DRD2, DAT, CCK, MTHFR and successful and safe treatment of Parkinson's disease are presented.
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PMID:[Pharmacogenetics in Parkinson's disease treatment]. 1851 70

Levodopa (L-dopa) treatment of Parkinson's disease (PD) is associated with elevated homocysteine (Hcy). To examine the relationship between Hcy, methylenetetrahydrofolate reductase polymorphisms (MTHFR: 677C/T; 1298A/C), and B-vitamins in older PD patients and whether Hcy or MTHFR polymorphisms were associated with clinical measures. MTHFR polymorphisms, B-vitamin intake, and blood concentrations of Hcy, vitamin B12 and folate, and creatinine were determined and compared between groups (PD and controls). The relationship of Hcy to clinical measures was examined in PD. Among 51 patients [30M/21F, mean age (SD): 71.5 (4.7)] and 50 controls [29M/21F, 71.5 (4.8)], Hcy was higher in PD [13.6 (3.8); controls: 10.5 (2.5), P < 0.0005]. Hcy was associated with B-vitamin intake [F = 21.7, P < 0.0005], folate level (R = 0.31, P = 0.035), and the interaction of intake with MTHFR 677T (F = 5.2, P = 0.007), but not MTHFR 1298C genotype. Hcy did not correlate with global measures of cognition, mood, or parkinsonism in PD or with dyskinesias, fluctuations, or freezing. Higher vitamin B12 levels were associated with lower dyskinesia risk. Hcy was influenced by PD, MTHFR 677 genotype, and vitamin use, but not by the MTHFR 1298 genotype. There was no clear association with motor or cognitive measures, but dyskinesias were less likely with higher B12.
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PMID:Homocysteine is not associated with global motor or cognitive measures in nondemented older Parkinson's disease patients. 1895 34

The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients (P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either.
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PMID:Homocysteine and cognitive impairment in Parkinson's disease: a biochemical, neuroimaging, and genetic study. 1945 54

Hyperhomocysteinaemia was reported in patients with Parkinson's disease (PD) treated with l-Dopa. The increase in plasma concentration of this sulfur compound arises from the massive methylation of the drug operated by the enzyme catechol-O-methyltransferase (COMT), which acts as a powerful sink of methyl groups. The contemporary occurrence of C677T polymorphism in homozygosity, leading to a temperature-labile variant of the MTHFR enzyme, induces an even more marked increase in tHcy. Here we show that l-Dopa administration in hyperhomocysteinemic PD patients is able to lower intracellular concentration of S-Adenosylmethionine (AdoMet) in erythrocytes (RBC), while the occurrence of hyperhomocysteinaemia causes a significant increase in S-Adenosylhomocysteine (AdoHcy) level. In patients with PD treated with l-Dopa and hyperhomocysteinemic, the remarkable decrease in AdoMet and the concurrent increase in AdoHcy concentration both contribute to significantly lower the transmethylation potential ([AdoMet]/[AdoHcy]), a useful index of the effectiveness of methyl group transfer by methyltransferases. This decrease could indeed contribute to partly attenuate, through a self-limiting kinetic mechanism, the tendency of developing drug resistance, partly mediated in these patients by COMT upregulation. Our results also support the conclusion that COMT inhibitors (entacapone or tolcapone), when administered in PD patients treated with l-Dopa, may potentiate the endogenous AdoHcy-dependent COMT inhibition mechanism already operative in a variable fashion.
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PMID:Impaired transmethylation potential in Parkinson's disease patients treated with L-Dopa. 1990 87

The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case-control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel-Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR=1.212 for T allele, 95% CI=1.097-1.340, p-value=0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR=1.187 for T allele, 95% CI=1.058-1.332, p-value=0.004) and Asian samples (allelic model, pooled OR=1.293 for T allele, 95% CI=1.058-1.580, p-value=0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value=0.0149) and CHB (Chinese, p-value=0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD.
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PMID:Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease. 2391 22


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