Association of ARNTL and PER1 genes with Parkinson's disease: a case-control study of Han Chinese.
Circadian disruptions may result in sleep problems, oxidative stress and an altered inflammatory response. These symptoms may contribute to PD pathogenesis, despite a lack of direct experimental evidence supporting this relationship. Clock genes are essential to drive and maintain circadian rhythm. To elucidate the possible role of circadian disruptions in PD, we investigated 132 tag variants in eight clock genes. We genotyped these tags within 1,394 Chinese cases and 1,342 controls using Illumina GoldenGate chips. We discovered that SNPs in ARNTL (rs900147, P = 3.33 × 10(-5), OR = 0.80) and PER1 (rs2253820, P = 5.30 × 10(-6), OR = 1.31) genes are significantly associated with PD risk. Moreover, the positive association of the ARNTL rs900147 variant was more robust in tremor dominant (TD) (P = 3.44 × 10(-4)) than postural instability and gait difficulty (PIGD) cases (P = 6.06 × 10(-2)). The association of the PER1 rs2253820 variant was more robust in PIGD (P = 5.42 × 10(-5)) than TD cases (P = 4.2 × 10(-2)). Haplotype analysis also showed that ARNTL and PER1 were associated with PD. Imputation analysis identified more SNPs within ARNTL and PER1 associated with PD, some of which may affect gene expression through altering the transcription factor binding site. In summary, our findings suggest that genetic polymorphisms in ARNTL and PER1 genes, as well as circadian disruptions, may contribute to PD pathogenesis.
Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100053, P.R. China.
Zhuqin
Z
Gu
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.|National Research Institute for Family Planning, Beijing 100081, P.R. China.
BinBin
B
Wang
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Yong-Biao
YB
Zhang
Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100053, P.R. China.
Hui
H
Ding
Department of Neurology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100053, P.R. China.
Yanli
Y
Zhang
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.|National Research Institute for Family Planning, Beijing 100081, P.R. China.
Jun
J
Yu
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Mingliang
M
Gu
Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100053, P.R. China.|Department of Neurology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100053, P.R. China.
Piu
P
Chan
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.|Department of Neurology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100053, P.R. China.
Yanning
Y
Cai
D056930:ARNTL Transcription Factors / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics*; D056926:CLOCK Proteins / Q000235:genetics; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D056950:Period Circadian Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D009687:Nuclear Proteins; C539022:PER1 protein, human; D056950:Period Circadian Proteins; D056926:CLOCK Proteins