Monoamine oxidase B gene and Cytochrome P450 2D6 gene polymorphism in sporadic Korean Parkinson's disease

Lee, Yong Hee; Lim, Jeong Geun; Yi, Sang Doe; Lee, Young Jae

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.