genetic regulation of α-synuclein mrna expression in various human brain tissuesα-synuclein mrna表达的基因调控在不同的人类大脑组织.pdfVIP

Genetic Regulation of a-Synuclein mRNA Expression in Various Human Brain Tissues 1 1 1 1 2,3 Colton Linnertz , Laura Saucier , Dongliang Ge , Kenneth D. Cronin , James R. Burke , Jeffrey N. 3 3 3 1,2,3 Browndyke , Christine M. Hulette , Kathleen A. Welsh-Bohmer , Ornit Chiba-Falek * 1 Institute for Genome Sciences Policy, Duke University Medical Center, Durham, North Carolina, United States of America, 2 Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America, 3 Joseph and Kathleen Bryan Alzheimer’s Disease Research Center, Duke University Medical Center, Durham, North Carolina, United States of America Abstract Genetic variability across the SNCA locus has been repeatedly associated with susceptibility to sporadic Parkinson’s disease (PD). Accumulated evidence emphasizes the importance of SNCA dosage and expression levels in PD pathogenesis. However whether genetic variability in the SNCA gene modulates the risk to develop sporadic PD via regulation of SNCA expression remained elusive. We studied the effect of PD risk-associated variants at SNCA 59 and 39regions on SNCA-mRNA levels in vivo in 228 human brain samples from three structures differentially vulnerable to PD pathology (substantia-nigra, temporal- and frontal-cortex) obtained from 144 neurologically normal cadavers. The extensively characterized PD- associated promoter polymorphism, Rep1, had an effect on SNCA-mRNA levels. Homozygous genotype of the ‘protect