MDR1 C3435T polymorphism and interaction with environmental factors in risk of Parkinson's disease: A case-control study in Japan

Chikako Kiyohara, Yoshihiro Miyake, Midori Koyanagi, Takahiro Fujimoto, Senji Shirasawa, Keiko Tanaka, Wakaba Fukushima, Satoshi Sasaki, Yoshio Tsuboi, Tatsuo Yamada, Tomoko Oeda, Hiroyuki Shimada, Nobutoshi Kawamura, Nobutaka Sakae, Hidenao Fukuyama, Yishio Hirota, Masaki Nagai

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Abstract

It has been suggested that P-glycoprotein (P-gp), the product of multidrug resistance 1 (MDR1) gene, regulates the brain entry of various xenobiotics. Impaired function of P-gp may be associated with an increased risk of Parkinson's disease (PD). The aim of this study was to investigate the impact of a MDR1 C3435T polymorphism on PD risk alone or in combination with environmental factors. A total of 238 patients with PD and 368 controls were genotyped for the MDR1 C3435T polymorphism. Subjects with the TT genotype of the C3435T polymorphism showed a nonsignificantly increased risk of PD [odds ratio (OR) = 1.49, 95% confidence interval (CI) = 0.85-2.25] compared with those with the CC genotype. A gene-environment interaction was suggested, with a combination of at least one T allele and ever drinking conferring significantly higher risk (OR = 1.83, 95% CI = 1.07-3.15, p = 0.029), compared with the CC genotype and never drinking. No significant interaction of smoking or occupational pesticide use with the C3435T polymorphism was observed. Our results suggest that the C3435T polymorphism may not play an important role in PD susceptibility in Japanese. Evidence of an interaction between the C3435T polymorphism and alcohol consumption was suggested.

Original languageEnglish
Pages (from-to)138-143
Number of pages6
JournalDrug metabolism and pharmacokinetics
Volume28
Issue number2
DOIs
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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    Kiyohara, C., Miyake, Y., Koyanagi, M., Fujimoto, T., Shirasawa, S., Tanaka, K., Fukushima, W., Sasaki, S., Tsuboi, Y., Yamada, T., Oeda, T., Shimada, H., Kawamura, N., Sakae, N., Fukuyama, H., Hirota, Y., & Nagai, M. (2013). MDR1 C3435T polymorphism and interaction with environmental factors in risk of Parkinson's disease: A case-control study in Japan. Drug metabolism and pharmacokinetics, 28(2), 138-143. https://doi.org/10.2133/dmpk.DMPK-12-RG-075