Novel and functional ABCB1 gene variant in sporadic Parkinson's disease

被引:15
作者
Li, Yuequn [1 ]
Li, Yonghua [2 ]
Pang, Shuchao [3 ]
Huang, Wenhui [3 ]
Zhang, Aimei [4 ]
Hawley, Robert G. [5 ,6 ]
Yan, Bo [3 ,5 ,6 ]
机构
[1] Jining Med Univ, Affiliated Hosp, Div Transcranial Doppler Ultrasound, Jining 272029, Shandong, Peoples R China
[2] Jining Med Univ, Affiliated Hosp, Div Ophthalmol, Jining 272029, Shandong, Peoples R China
[3] Jining Med Univ, Affiliated Hosp, Shandong Prov Key Lab Cardiac Dis Diag & Treatmen, Jining 272029, Shandong, Peoples R China
[4] Jining Med Univ, Affiliated Hosp, Div Neurol, Jining 272029, Shandong, Peoples R China
[5] George Washington Univ, Dept Anat & Regenerat Biol, Washington, DC 20037 USA
[6] Jining Med Univ, Affiliated Hosp, Shandong Prov Sino US Cooperat Ctr Translat Med, Jining 272029, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
Parkinson's disease; ABCB1; Promoter; DNA sequence variants; BLOOD-BRAIN-BARRIER; MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN EXPRESSION; MDR1; GENE; DRUG-RESISTANCE; PROMOTER REGION; BREAST-CANCER; CELL-LINES; POLYMORPHISM; TRANSPORTER;
D O I
10.1016/j.neulet.2014.02.025
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 ABCBI 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:61 / 66
页数:6
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