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Genetic association between cytochrome P450IA1 gene and susceptibility to Parkinson's disease

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Summary

Idiopathic Parkinson's disease (PD) is a multifactorial neurodegenerative disorder resulting from environmental factors acting on genetically susceptible individuals with normal aging. Cytochrome P450IA1 is a dioxin-inducible enzyme which is responsible for the activation of procarcinogens and environmental pollutants, such as benzo[α]pyrene and other aromatic hydrocarbons. The frequencies of polymorphic alleles of cytochrome P450IA1 gene (CYPIA1) were studied in 126 unrelated patients with PD in comparison with 176 healthy Japanese. The frequency of the Msp I polymorphic allele, a variant of CYPIA1 (m2), was significantly higher in patients with PD (0.444) than in controls (0.349). The risk of PD in homozygotes for m2 was 2.34-fold greater than homozygotes for the wild-type, ml. The relative risk for PD in homozygotes for CYPIA1Val was 6.54-fold higher than in homozygotes for the wild type (CYPIA1Ile)(p < 0.001). These results strongly suggest that the CYPIA1 might be one of the susceptibility genes for PD.

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References

  • Catteau A, Douriez E, Beaune P, Poisson N, Bonaiti-Pellie C, Laurent P (1995) Genetic polymorphism of induction of CYPIA1 (EROD) activity. Pharmacogenetics 5: 110–119

    Google Scholar 

  • Clarke PBS, Hommer DW, Pert A, Skirboll LR (1985) Electrophysiological action of nicotine on substantia nigra single units. Br J Pharmacol 85: 827–835

    Google Scholar 

  • Farin FM, Omiecinski CJ (1993) Regionspecific expression of cytochrome P450s and microsomal epoxide hydrolase in human brain tissue. J Toxicol Environ Health 40: 323–341

    Google Scholar 

  • Ghersi-Egea J-F, Perrin R, Leininger-Muller B, Grassiot M-C, Jeandel C, Floquet J, Cuny G, Siest G, Minn A (1993) Subcellular localization of cytochrome P450, and activities of several enzymes responsible for drug metabolism in the human brain. Biochem Pharmacol 45: 647–658

    Google Scholar 

  • Golbe LI, Cody RA, Duvoisin RC (1986) Smoking and Parkinson's disease. Search for a dose-response relationship. Arch Neurol 43: 774–778

    Google Scholar 

  • Gonzalez FJ (1988) The molecular biology of cytochrome P450s. Pharmacol Rev 40: 243–288

    Google Scholar 

  • Gonzalez FJ, Gelboin HV (1994) Role of human cytochrome P450 in the metabolic activation of chemical carcinogens and toxins. Drug Metab Rev 26: 165–183

    Google Scholar 

  • Hayashi J-I, Watanabe J, Nakachi K, Kawajiri K (1991) Genetic linkage of lung cancer-associated Msp I polymorphisms with amino acid replacement in the heme-binding region of the human cytochrome P450 A1 gene. J Biochem 110: 407–411

    Google Scholar 

  • Kadlubar FF (1994) Biochemical individuality and its implications for drug and carcinogen metabolism. Recent insights from acetyltransferase and cytochrome P450IA2 phenotyping and genotyping in humans. Drug Metab Dispos 26: 37–46

    Google Scholar 

  • Kondo K, Kurland LT, Schull WJ (1973) Parkinson's disease, genetic analysis and evidence of a multifactorial etiology. Mayo Clin Proc 48: 465–475

    Google Scholar 

  • McConkey DJ, Hartzell P, Duddy SK, Hakansson H, Orrenius S (1989) 2,3,7,8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation. Science 242: 256–259

    Google Scholar 

  • McKusick VA (1994) Cyrochrome P-450, Family I, P3-450 [CYPIA2; dioxin-inducible P3-450 phenacetin metabolism, defect in induced phenacetin o-deethylase, deficiency of induced] in Medelian inheritance in man. The Johns Hopkins University Press, Baltimore London, p 401, I

    Google Scholar 

  • McManus ME, Burgess WM, Veronese ME, Huggett A, Quattrochi LC, Tukey RH (1990) Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochromes P450. Cancer Res 50: 3367–3376

    Google Scholar 

  • Morens DM, Grandinetti A, Reed D, White LR, Ross GW (1995) Cigarette smoking and protection from Parkinson's disease: false association or etiologic clue? Neurology 45: 1041–1051

    Google Scholar 

  • Nebert DW, Petersen DD, Puga A (1991) Human AH locus polymorphism and cancer: inducibility of CYPIA1 and other genes by combustion products and dioxin. Pharmacogenetics 1: 68–78

    Google Scholar 

  • Okada T, Kawashima K, Fukushi S, Minakuchi T, Nishimura S (1994) Association between a cytochrome P450 CYPIA1 genotype and incidence of lung cancer. Pharmacogenetics 4: 333–340

    Google Scholar 

  • Paulson GW (1992) Addiction to nicotine is due to high intrinsic levels of dopamine. Med Hypotheses 38: 206–207

    Google Scholar 

  • Petersen DD, McKinney CE, Ikeya K, Smith HH, Bale AE, McBride OW, Nebert DW (1991) Human CYPIA1 gene: cosegregation of the enzyme inducibility phenotype and an RFLP. Am J Hum Genet 48: 720–725

    Google Scholar 

  • Quattrochi LC, Okino ST, Pendurthi UR, Tukey RH (1985) Cloning and isolation of human cytochrome P-450 cDNAs homologous to dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6. DNA 4: 395–400

    Google Scholar 

  • Schwart RD, Kellar KJ (1983) Nicotinic cholinergic receptor binding sites in the brain: regulation in vivo. Science 220: 214–216

    Google Scholar 

  • Smith CAD, Gough AC, Leigh PN, Summers BA, Harding AE, Maranganore DM, Sturman SG, Schapira AHV, Williams AC, Spurr NK, Wolf CR (1992) Debrisoquine hydroxylase gene polymorphism and susceptibility to Parkinson's disease. Lancet 339: 1375–1377

    Google Scholar 

  • Wedlund PJ, Kimura S, Gonzalez FJ, Nebert DW (1994) I462V mutation in the human CYPIA1 gene: lack of correlation with either Msp I 1.9kb (M2) allele or CYPIA1 inducibility in a three-generation family of east Mediterranean descent. Pharmacogenetics 4: 21–26

    Google Scholar 

  • Wright SC, Zhong J, Zheng H, Larrick JW (1993) Nicotine inhibition of apoptosis suggests a role in tumor promotion. FASEB J 7: 1045–1051

    Google Scholar 

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Takakubo, F., Yamamoto, M., Ogawa, N. et al. Genetic association between cytochrome P450IA1 gene and susceptibility to Parkinson's disease. J. Neural Transmission 103, 843–849 (1996). https://doi.org/10.1007/BF01273362

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  • DOI: https://doi.org/10.1007/BF01273362

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