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Polymorphism in environment responsive genes and association with Parkinson disease

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Abstract

Attempts were made in the present case-control study to investigate the association of polymorphism in the genes encoding proteins involved in toxication–detoxication and dopaminergic pathways and susceptibility to Parkinson’s disease (PD). Seventy patients suffering from PD and one hundred healthy controls belonging to the same geographical location and same ethnicity were included in the study. PCR-RFLP and allele-specific PCR-based methodology were used to identify the genotypes. Multivariate logistic regression analysis revealed that heterozygous genotypes of cytochrome P4502D6*4(CYP2D6*4), CYP2E1*5B (RsaI) polymorphism and homozygous mutant genotypes of CYP2E1*6 (Dra1) were found to be overrepresented in PD cases when compared to the controls. Risk was also found to be increased in patients carrying glutathione S-transferase T1 (GSTT1) null or homozygous variant genotypes of GSTP1. Significant association was observed for monoamine oxidase-B(MAO-B) variant allele G and PD, whereas no difference in genotype and allele frequencies was observed for manganese-superoxide dismutase (MnSOD), dopamine receptor-D2(DRD2), and dopamine transporter (DAT) genes between controls and PD cases. Genotype combinations characterized by the presence of two variant genotypes on their corresponding loci revealed that four combinations of GSTT1 null and MnSOD(-9Val) or GST null and MAOB-G or CYP2E1*5B and MAO-B-AG or CYP2E1*5B and DRD2 (Taq1A-het) genotypes in the patients exhibited severalfold higher and significant association with risk to PD. Our data suggest that polymorphism in the genes involved in detoxification and dopamine regulation may modulate the susceptibility to PD and could be important risk factors in the pathogenesis of PD.

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Acknowledgments

The authors are grateful to Director, Industrial Toxicology Research Centre, Lucknow, for his keen interest and support in carrying out the study. Ms. Madhu Singh is grateful to CSIR, New Delhi, for providing Senior Research Fellowship. The financial support of Indian Council of Medical research (ICMR) in sponsoring a research project for carrying out the above studies is gratefully acknowledged. The technical assistance of Mr. B.S. Pandey and Mr. Rajesh Misra and computer help of Mr. Mohd. Aslam is gratefully acknowledged. ITRC communication No.2602.

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Authors and Affiliations

  1. Developmental Toxicology Division, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow, 226 001, India

    Madhu Singh, Anwar J. Khan, Parag P. Shah, Rakesh Shukla, V. K. Khanna & Devendra Parmar

  2. Department of Neurology, King George’s Medical University, Shahmina Road, Lucknow, 226 001, India

    Rakesh Shukla

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  1. Madhu Singh
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Correspondence to Devendra Parmar.

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Singh, M., Khan, A.J., Shah, P.P. et al. Polymorphism in environment responsive genes and association with Parkinson disease. Mol Cell Biochem 312, 131–138 (2008). https://doi.org/10.1007/s11010-008-9728-2

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