Naslov
Multiplex Allele-Specific PCR in the Study of Association Between CYP2D6 Polymorphism and Parkinson´s Disease

Autori
Štefanović, Mario ; Topić, Elizabeta ; Ivanišević, Ana-Maria ; Koršić, Marta ; Relja, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Human genomics The basis of the medicine of tomorrow, Second Conference: Validating and Using Pharmacogenomics / Siest, Gerard - Basel : Roche diagnostics, 2000

Skup
Human Genomics,Second Joint Conference of IFCC-Roche Diagnostics: Validating and Using Pharmacogenomics

Mjesto i datum
Kyoto, Japan, 16.04.2000. - 19.04.2000

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
CYP2D6 polymorphism; Parkinson's disease

Sažetak
Parkinson’s disease (PD) is characterized by a progressive neuronal degradation caused by interaction of genetic susceptibility, environmental factors and, to a lesser extent, aging (1). The susceptibility to PD has been related to the genetic polymorphism of the CYP2D6 enzyme, involved in the metabolism of environmental neurotoxins. Several studies indicate that subjects carrying CYP2D6 alleles containing inactivating mutations are at a higher risk for the development of Parkinson’s disease. Most frequently variant alleles *3, *4 and *6 have been described in association with susceptibility to PD (2). The aim of this study was to investigate the association of CYP2D6 polymorphism of inactivating alleles with PD by multiplex allele-specific PCR. After obtaining informed consent, 50 PD patients and 60 healthy volunteers of the same ethnic group were included in the study. Genomic DNA from peripheral leukocytes of PD patients and healthy controls was extracted by the salting-out method. The analyses for mutation of the CYP2D6 gene locus were performed by multiplex-allele specific PCR permitting simultaneous identification of six defective alleles (CYP2D6*3,*4,*5,*6,*7 and *8) amplified with a different set of primers. The phenotype was predicted as extensive metabolizer (EM, two wild-type alleles), intermediate metabolizer (IM, one deficiency and one wild type allele) and poor metabolizer (PM, two deficiency alleles) (3). Chi squared analysis was used to compare allelic frequencies, and genotype and phenotype distribution between PD and control subjects. Only mutant alleles 2D6*3, *4, and *6 were found in both control and PD patient groups. The allelic frequencies found in the control (1.4% 2D6*3; 15.0% *4; 0.7% *6) and PD group (1.3% 2D6*3; 28.9% *4 and 1.3% *6) did not differ significantly (p=0.816). A statistically significant difference (p=0.004) was observed in genotype distribution between the control and PD patients. In controls 2.9% of 2D6*3, 22.9% of 2D6 *4 and 1.4% of 2D6 *4/*6 heterozygous genotype and 2.9% of 2D6*4 homozygous genotype were found. In PD group 2.6% of 2D6*3, 42.1% of *4 and 2.6% of *6 heterozygous genotype and 7.9% of 2D6*4 homozygous genotype were found. The predictable phenotype distribution found in the control and PD group was significantly different, too (p=0.002). In the control group 25.7% of subjects were characterized as IM and 4.3% as PM phenotype. In PD patients the frequency of IM phenotype was 47.4%, and of PM phenotype 7.9%. The odds ratio for IM and PM was 2.60 and 1.91, respectively. The results of this study demonstrate an association of the CYP2D6 mutant alleles with PD resulting in an approximate odds ratio of 2 for PD in the individuals carrying these markers of poor debrisoquin metabolism.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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