Effect of MTHFR Polymorphisms on Hyperhomocysteinemia in Levodopa-treated Parkinsonian Patients

Abstract

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.

The 894G > T (Glu298Asp) Variant in the Endothelial NOS Gene and MTHFR Polymorphisms Influence Homocysteine Levels in Patients with Cognitive Decline

“…In line with previously reported observations in patients affected by cognitive decline or other neurological disorders (Caccamo et al 2004(Caccamo et al , 2007Gorgone et al 2009a, b), our CIPs with MTHFR TT677 genotype had significantly higher plasma Hcy levels than controls having the same genotype or patients having other MTHFR genotypes.…”

Methylenetetrahydrofolate reductase polymorphisms and plasma homocysteine in levodopa-treated and non-treated Parkinson's disease patients

“…This may perhaps explain why the increased Hcy levels (mean value, 13.16 μmol/L) were only slightly higher, compared to the reference ranges in our laboratory (4.45-12.42 μmol/L). Also, our results may be compatible with previous reports, which established a positive correlation between the Hcy level and daily levodopa dose [4,21,28]. However, this correlation was not displayed in the present study (p=0.486).…”

“…These findings further imply that the 677T allele, not 1298A/A, really promotes Hcy level elevations. Recently, a similar comparison performed on levodopa-treated PD and healthy subjects obtained comparable results [21]. Likewise, that study revealed a remarkable Hcy level elevation in T/T + A/A, intermediate elevation in C/T with either A/A or A/C, and suggested a protective effect of C/C + A/A against Hcy elevation in treated patients [21].…”

“…The other study compared PD patients (mostly treated with levodopa) with healthy controls, and suggested that Hcy level was affected by the interaction of B-vitamin intake and 677T, but not by the 1298C genotype [20]. However, the influence of connecting C677T and A1298C polymorphisms and levodopa therapy on plasma Hcy levels in PD patients has not been clearly established [21].…”

Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson’s disease

“…A different distribution of the polymorphism of the methylenetetrahydrofolate reductase (MTHFR) in the investigated cohorts could be one reason for these inconsistent results (Nakaso et al 2003;Caccamo et al 2007). In particular, the homozygote MTHFR T/T allele predisposes for an elevation of homocysteine concentrations, but these findings are also under debate in PD patients (Nakaso et al 2003;Caccamo et al 2007). Nearly all investigators performed an overnight withdrawal of PD drugs before blood sampling for homocysteine determination or do not describe the modes of blood sampling in detail.…”