title: CHRNB3 c.-57A>G functional promoter change affects Parkinson's disease and smoking.
abstract: Cigarette smoking is protective in Parkinson's disease (PD), possibly because of nicotine action on brain nicotinic-acetylcholine receptors. The β3 nicotinic-acetylcholine receptor subunit (encoded by CHRNB3) is depleted in the striatum of PD patients and associated with nicotine dependence. Herein, the CHRNB3 gene was sequenced, and the c.-57G allele frequency was 0.31 and 0.26 among patients (n = 596) and controls (n = 369), respectively (p = 0.02, odds ratio = 1.33, 95% confidence interval = 1.03-1.73). The c.-57G allele was strongly associated with smoking in patients, as 48.4% of c.-57G carriers compared with 32.6% of noncarriers reported smoking history (p < 0.0001). The transcription factor Oct-1 binding was almost eliminated in lymphoblasts with the c.-57G/G genotype, to only 6.5% percent, and the CHRNB3 promoter activity was reduced in cells with the c.-57G/G genotype by 96%-70%. These findings suggest that the CHRNB3 c.-57A>G alteration affects the promoter activity and is associated with PD and smoking in PD patients. It is therefore possible that nicotine may be valuable for patients who carry this alteration and beneficial in PD only for patients with specific genotypes.
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Bar-Shira
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Mali
authors.initials: M
authors.lastname: Gana-Weisz
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Gan-Or
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Eytan
authors.initials: E
authors.lastname: Giladi
authors.affiliation: The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Movement Disorders Unit, Parkinson Center, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Giladi
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: aviorr@tasmc.health.gov.il.
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
mesh_terms: D000368:Aged; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000627:therapeutic use; D050811:Octamer Transcription Factor-1; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000235:genetics*; D012907:Smoking / Q000235:genetics*
chemical_list: C539371:CHRNB3 protein, human; D050811:Octamer Transcription Factor-1; D011978:Receptors, Nicotinic; D009538:Nicotine
keywords: CHRNB3; Genetics; Parkinson's disease; Smoking; β3 nicotinic-acetylcholine receptor subunit