The effect of monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) polymorphisms on levodopa therapy in patients with sporadic Parkinson's disease.
OBJECTIVE
The etiology of sporadic idiopathic Parkinson's disease (PD) is considered multifactorial with both genetic and environmental factors modifying the disease expression. Recent studies suggest that polymorphism in monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) might influence the risk and treatment of PD. The aim of the study was to evaluate the effect of MAOB and COMT genetic polymorphism on effective daily dose of levodopa applied during the first 5 years of treatment, and to find out if a relationship exists between MAOB and COMT haplotypes and motor disturbances onset in PD patients treated with levodopa preparations.


METHODS
A total of 95 patients (40 females and 55 males) of Polish origin diagnosed with sporadic PD were enrolled into the study, and were divided into two groups. Group 1 - patients treated with doses of levodopa below 500 mg/day during the first 5 years of treatment. Group 2 - patients requiring levodopa doses exceeding 500 mg/24 h during the first 5 years of treatment. Low activity alleles of MAOB and COMT, i.e. MAOB allele A and COMT(L) as well as high activity ones, i.e. MAOB allele G and COMT(H), were determined using PCR-RFLP method.


RESULTS
No statistically significant differences were found in MAOB and COMT allele distribution in the two groups. However, the frequency of COMT(L/L) homozygotes was higher in the group treated with low doses of levodopa when compared with the second group. MAOB and COMT AG-HH haplotype predominated in the group of females treated with high daily doses of levodopa when compared with AG-LL haplotype in the group of females treated with low daily doses of levodopa (<500 mg/24 h).


CONCLUSIONS
The results of the study suggest that patients with COMT(L/L) genotype and possibly MAOB genotype A may benefit from more efficient and safer levodopa therapy.
Białecka
M
M
Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin.
Droździk
M
M
Kłodowska-Duda
G
G
Honczarenko
K
K
Gawrońska-Szklarz
B
B
Opala
G
G
Stankiewicz
J
J
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006239:Haplotypes; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012189:Retrospective Studies
D000978:Antiparkinson Agents; D007980:Levodopa; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase