Affiliations: Developmental Toxicology Division, Indian Institute of
Toxicology Research (Formerly: Industrial Toxicology Research Centre), CSIR,
P.O. Box 80, M.G. Marg, Lucknow 226 001, India | Department of Neurology, Chhatrapati Shahuji Maharaj
Medical University, Shahmina Road, Lucknow 226 001, India
Note: [] Corresponding author: Dr. Devendra Parmar, Developmental
Toxicology Division, Indian Institute of Toxicology Research, Council of
Scientific & Industrial Research, P.O. Box 80, M. G. Marg, Lucknow 226
001, India. Tel.: +91 0522 2620207, Ext. 261; Fax: +91 522 2628227; E-mail:
[email protected]
Abstract: 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.
