LRRK2 Gly2385Arg polymorphism, cigarette smoking, and risk of sporadic Parkinson's disease: A case-control study in Japan

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

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17 Citations (Scopus)

Abstract

Previous case-control studies in Japanese and ethnic Chinese populations reported that the LRRK2 Gly2385Arg variant is a risk factor for Parkinson's disease (PD). We aimed to validate the previous findings and investigate whether cigarette smoking influences the relationship between the Gly2385Arg variant and PD. Included were 229 cases within 6 years of onset of sporadic PD. Controls were 358 inpatients and outpatients without a neurodegenerative disease. The frequency of the heterozygous genotype was 13.1% of cases and 6.4% of controls: adjusted OR for the GA genotype was 2.06 (95% CI: 1.15-3.69). Compared with subjects with the GG genotype who had ever smoked, those with the GA genotype who had never smoked had a 5.8-fold increased risk of sporadic PD. The multiplicative interaction between the SNP and smoking was not statistically significant. With respect to the additive interaction, the estimated attributable proportion due to interaction (AP), but not relative excess risk due to interaction or the synergy index, was statistically significant (AP = 0.50, 95% CI: 0.05-0.94), suggesting the presence of a biological interaction. The present study confirms that the LRRK2 Gly2385Arg variant is a risk factor for sporadic PD. In addition, we provide new evidence for the biological interaction between the polymorphism and smoking with regard to the risk of sporadic PD.

Original languageEnglish
Pages (from-to)15-18
Number of pages4
JournalJournal of the Neurological Sciences
Volume297
Issue number1-2
DOIs
Publication statusPublished - Oct 15 2010

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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