Methylenetetrahydrofolate reductase polymorphisms and plasma homocysteine in levodopa-treated and non-treated Parkinson's disease patients.
Genetic C677T and A1298C polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) and levodopa therapy in Parkinson's disease (PD) may increase homocysteine (Hcy) level. We examined whether connecting both polymorphisms influences the effect of levodopa on Hcy. MTHFR genotypes and Hcy, vitamin B(12), and folate levels were determined in 48 levodopa-treated PD patients (PD-L), 28 non-treated PD patients (PD-N) and 110 controls. Hcy was remarkably higher in PD-L than in PD-N and controls (p<0.001); similarly, the differences were seen in different age subgroups and in both genders. Furthermore, Hcy differences between PD-L and PD-N were evident in 677C/T, T/T, C/T + A/A, T/T + A/A (all p<0.05), and 1298A/A (p<0.001), but not in others such as 677C/C, and C/C + A/A. Hcy in PD-N and controls was comparable for all genotypes. In PD-L, Hcy was the highest in 677T/T, then in C/T, and in C/C with a significant difference from T/T (p=0.014), but was not different among A1298C genotypes. Likewise, Hcy was the highest in 677T/T+1298A/A, intermediate in C/T+A/A, and the lowest in C/C+A/A. In PD-N, Hcy was similar among all genotypes. In conclusion, Hcy elevation may be caused by levodopa administration, and further promoted by 677C/T and T/T, but not by A1298C genotypes. The promoting elevation in 1298A/A is attributed to combining the 677T allele. Neither C677T nor A1298C genotypes contribute to elevating Hcy in PD-N.
Department of Neurology, Taipei Medical University Hospital, Taipei, Taiwan.
Rey-Yue
RY
Yuan
Jau-Jiuan
JJ
Sheu
Jia-Ming
JM
Yu
Chaur-Jong
CJ
Hu
Ing-Jy
IJ
Tseng
Chun-Sum
CS
Ho
Ching-Ying
CY
Yeh
Ya-Lin
YL
Hung
Tsuey-Ru
TR
Chiang
D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use; D001483:Base Sequence / Q000235:genetics; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+) / Q000235:genetics*; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017678:Sex Distribution
D000978:Antiparkinson Agents; D015415:Biomarkers; D005819:Genetic Markers; D006710:Homocysteine; D007980:Levodopa; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+)