title: Novel and functional ABCB1 gene variant in sporadic Parkinson's disease.
abstract: Parkinson's disease (PD) is a common progressive neurodegenerative disease. Most cases of PD are sporadic, which is caused by interaction of genetic and environmental factors. To date, genetic causes for sporadic PD remain largely unknown. ATP-binding cassette sub-family B member 1 (ABCB1) is a membrane-associated protein that acts as an efflux transporter for many substrates, including chemotherapeutic agents, anti-epilepsy medicine, antibiotics and drugs for PD. ABCB1 gene is widely expressed in human tissues, including endothelial cells of capillary blood vessels at blood-brain barrier sites. In PD patients, decreased ABCB1 levels have been reported. We speculated that misregulation of ABCB1 gene expression, caused by DNA sequence variants (DSVs) within its regulatory regions, may be involved in PD development. In this study, we genetically and functionally analyzed the proximal promoter of the human ABCB1 gene, which is required for constitutive expression, in sporadic PD patients and healthy controls. The results showed that a novel and heterozygous DSV g.117077G>A was identified in one PD patient, but in none of the controls. This DSV significantly altered the transcriptional activity of the ABCB1 gene promoter in transiently transfected HEK-293 cells. A heterozygous DSV g.116347T>C was only found in one control. Four single-nucleotide polymorphisms, g.116154T>C (rs28746504), g.117130A>G (rs2188524), g.117356C>G (rs34976462) and g.117372T>C (rs3213619), and one heterozygous deletion DSV g.116039del were found in PD patients and controls with similar frequencies. Therefore, our findings suggest that ABCB1 gene promoter DSVs may contribute to PD development as a rare risk factor.
authors.affiliation: Division of Transcranial Doppler Ultrasound, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Yuequn
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Ophthalmology, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Shuchao
authors.initials: S
authors.lastname: Pang
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Huang
authors.affiliation: Division of Neurology, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Regenerative Biology, The George Washington University, 2300 Eye Street, NW Washington DC 20037, USA; Shandong Provincial Sino-US Cooperation Center for Translational Medicine, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China. Electronic address: rghawley@gwu.edu.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hawley
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China; Department of Anatomy and Regenerative Biology, The George Washington University, 2300 Eye Street, NW Washington DC 20037, USA; Shandong Provincial Sino-US Cooperation Center for Translational Medicine, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China. Electronic address: yanbo@mail.jnmc.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger
keywords: ABCB1; DNA sequence variants; Parkinson’s disease; Promoter