TY - JOUR
T1 - LRRK2 Gly2385Arg polymorphism, cigarette smoking, and risk of sporadic Parkinson's disease
T2 - A case-control study in Japan
AU - Miyake, Yoshihiro
AU - Tsuboi, Yoshio
AU - Koyanagi, Midori
AU - Fujimoto, Takahiro
AU - Shirasawa, Senji
AU - Kiyohara, Chikako
AU - Tanaka, Keiko
AU - Fukushima, Wakaba
AU - Sasaki, Satoshi
AU - Yamada, Tatsuo
AU - Oeda, Tomoko
AU - Miki, Takami
AU - Kawamura, Nobutoshi
AU - Sakae, Nobutaka
AU - Fukuyama, Hidenao
AU - Hirota, Yoshio
AU - Nagai, Masaki
N1 - Funding Information:
This study was supported by Health and Labour Sciences Research Grants, Research on Intractable Diseases, Research Committee on Epidemiology of Intractable Diseases from the Ministry of Health, Labour, and Welfare, Japan .
PY - 2010/10/15
Y1 - 2010/10/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jns.2010.07.002
DO - 10.1016/j.jns.2010.07.002
M3 - Article
C2 - 20673920
AN - SCOPUS:77956653820
SN - 0022-510X
VL - 297
SP - 15
EP - 18
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -