LRRK2 Gly2385Arg polymorphism, cigarette smoking, and risk of sporadic Parkinson's disease: a case-control study in Japan.
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 6years 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.
Miyake
Yoshihiro
Y
Department of Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. miyake-y@fukuoka-u.ac.jp
Tsuboi
Yoshio
Y
Koyanagi
Midori
M
Fujimoto
Takahiro
T
Shirasawa
Senji
S
Kiyohara
Chikako
C
Tanaka
Keiko
K
Fukushima
Wakaba
W
Sasaki
Satoshi
S
Yamada
Tatsuo
T
Oeda
Tomoko
T
Miki
Takami
T
Kawamura
Nobutoshi
N
Sakae
Nobutaka
N
Fukuyama
Hidenao
H
Hirota
Yoshio
Y
Nagai
Masaki
M
D000368:Aged; D001120:Arginine / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005998:Glycine / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000208:ethnology; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics* / Q000523:psychology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000235:genetics* / Q000523:psychology; D011795:Surveys and Questionnaires
D001120:Arginine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine