Monoamine oxidase B gene and Cytochrome P450 2D6 gene polymorphism in sporadic Korean Parkinson's disease.
- Author:
Yong Hee LEE
1
;
Jeong Geun LIM
;
Sang Doe YI
;
Young Jae LEE
Author Information
1. Department of Neurology, College of Medicine, Keimyung University, Dongsan Hospital, Taegu, Korea.
- Publication Type:Original Article
- Keywords:
Parkinson's disease;
Monoamine oxidase B;
CYP2D6;
Gene polymorphism
- MeSH:
Alleles;
Base Pairing;
Cytochrome P-450 CYP2D6*;
Cytochrome P-450 Enzyme System*;
Cytochromes*;
Debrisoquin;
Digestion;
DNA;
Dopamine;
Epidemiologic Studies;
Exons;
Genetic Predisposition to Disease;
Humans;
Introns;
Male;
Metabolism;
Monoamine Oxidase*;
Odds Ratio;
Parkinson Disease*;
Polymerase Chain Reaction;
Polymorphism, Restriction Fragment Length
- From:Journal of the Korean Neurological Association
1999;17(1):63-71
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Epidemiological studies have identified that positive family history and frequent exposures to environmental toxins such as 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) are of prime causative factors for PD. These toxins are mainly metabolized by MAO-B and CYP2D6. Thus, an individual with inherited defect in xenobiotic metabolism could have a higher susceptibility to PD. We performed this study to investigate a possible allelic association of MAO-B and CYP2D6 known to be involved in metabolism of dopamine and other drugs such as debrisoquine in PD. METHODS: We studied polymorphism of MAO-B and CYP2D6 genes in 69 sporadic idiopathic PD patients (31 males and 38 females) and 41 age-matched healthy control (20 males and 21 females) using genomic DNA extracted from peripheral blood white cell with polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP). RESULTS: There were eight different alleles of various numbers of GT repeats within the second intron of MAO-B. The frequency of (GT)20 allele was the highest (44.7%) in PD, while the frequencies of (GT)14 allele and (GT)19 allele were the highest in control groups. Furthermore, the odds ratios of (GT)16 allele and (GT)20 allele were 4.93 (95% confidence interval 0.6-107.63) and 6.15 (95% confidence interval; 2.52-15.51), respectively, suggesting a higher susceptibility to PD in (GT)20 allelic group (p<0.001). Polymorphism of CYP2D6 was also examined by PCR amplification followed by digestion with restriction enzymes. However, we were unable to identify G to A substitution at the junction of intron 3 and exon 4 nor base pair deletion in exon 5 from PD and control groups, which have been reported previously. CONCLUSIONS: These results suggest that the MAO-B gene polymorphism could serve as a determinant of genetic susceptibility to PD at least in Korean population. But the susceptibility may not be directly associated with polymorphism of CYP2D gene examined in this study.
