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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6

Fig. 1

Higher expression of SIRT6 is associated with Parkinson’s Disease in humans. a Six N-terminus SNPs in SIRT6 are in strong linkage disequilibrium (LD). LD evaluation of genotyped SNPs in SIRT6 is shown. Shading of diamonds and numbers depict LD between markers based on the R2 measure, where a value of “44” corresponds to R2 = 0.44; (b) A summary of the associations between SNPs in SIRT6, SIRT6 gene expression, and Parkinson’s disease prevalence. SNP ID, position, major - minor alleles and frequency (Freq.), the nominal p-value for the association of the SNP with the SIRT6 expression, and the corrected p-value for the SNP association with PD prevalence are presented. We find that SNPs associated with elevated expression of SIRT6, also associate with increased prevalence of PD. The analyzed dataset is derived from ROS-MAP cohorts [6], in which all participants are organ donors. The dataset had already been assembled into RPKM values based on ENSEMBL gene ID and is publicly available through online Synapse archive (accession # syn3219045). c SNP rs107251 is associated with elevated expression of SIRT6 in human brains, bar graph showing the minor C/T genotype has ~ 4-fold greater expression of SIRT6 then major C/C. d The 13 SIRT6 SNPs analyzed from A/B, plotted by association with Parkinson’s Disease by effect on SIRT6 expression. Note that the SNPs that associate the most significantly with expression (red) also have the strongest association with Parkinson’s. e Box plot of the expression of SIRT6 in the substantia nigra region between control and PD patients, data is deposited to NCBI, accession number GSE8397. f Representative SDS-PAGE analysis of brain tissue lysates from healthy controls, Parkinson’s Disease patients, and tobacco smokers. See Additional file 1: Figure S1 for full blots. g Box plot quantification of SIRT6 protein levels (relative to β-actin), such as those presented on (F). * denotes significant difference compared from controls, # denotes significance from Parkinson’s patients. Student’s two tailed T-Test p-value for controls vs PD = 0.04, controls vs heavy smokers = 0.02, PD vs smokers = 0.02, PD vs heavy smokers = 0.002. One-way ANOVA between all groups p-value = 0.0018. See Additional file 1: Figure S1 for full blots used for quantification. Heavy smokers used two or more packs of cigarettes per day. h Scatter plot showing the correlation between SIRT6 and TNFα protein abundance. Pearson correlation = 0.49 and the slope of regression p-value = 0.002. See Additional file 1: Figure S1 for blots. i Representative western blot showing the positive correlation between the levels of SIRT6 and TNFα, such as those presented in (h)

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