Association of polymorphism in cytochrome P450 2D6 and N-acetyltransferase-2 with Parkinson's disease.
The present case-control study was carried out to investigate the association of polymorphism in cytochrome P450 2D6 (CYP2D6) and N-acteyltransferase-2 (NAT2}, that are involved in the metabolism and detoxification of chemicals causing Parkinson disease (PD) like symptoms, with PD. Our data demonstrated increased frequency of CYP2D6*2 (1749G/C and 2938C/T), CYP2D6*4 (1934G/A) and CYP2D6*10A (188C/T) polymorphisms in PD cases when compared to the controls. Statistical analysis revealed the significant association of CYP2D6*4 (1934G/A) and CYP2D6*10A (188C/T) polymorphism with PD. Likewise, increased frequency of NAT2*7 polymorphism that leads to the slow acetylator phenotype was observed in PD patients with more than fivefold increased risk (OR: 5.55; 95% CI: 0.56-54). No change was observed in the frequency of NAT*5 or NAT*6 alleles in the cases. Further, cases carrying combination of heterozygous genotypes of CYP2D6*4 or CYP2D6*10A(188C > T) and NAT2*5 were found to be at significantly higher risk for PD demonstrating the importance of gene-gene interactions in determining susceptibility to PD.
Singh
Madhu
M
Developmental Toxicology Division, Indian Institute of Toxicology Research (Formerly: Industrial Toxicology Research Centre), CSIR, PO Box 80, MG Marg, Lucknow 226 001, India.
Khanna
Vinay K
VK
Shukla
Rakesh
R
Parmar
Devendra
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
D005819:Genetic Markers; D019389:Cytochrome P-450 CYP2D6; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human