Differential expression of α-synuclein splice variants in the brain of alcohol misusers: Influence of genotype

Abstract

Please cite this article as: Janeczek, P., Brooker, C., Lewohl, P.D.,J.M., Differential Expression of rmalpha-Synuclein Splice Variants in the Brain of Alcohol Misusers: Influence of Genotype, Drug and Alcohol Dependence (2015), http://dx.doi.org/10. 1016/j.drugalcdep.2015.05.045 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Allele and genotype frequencies differed significantly between alcohol misusers and controls for three SNPs, rs356221, rs356219 and rs2736995. Two SNPs, rs356221 and rs356219, were in high linkage disequilibrium. There was no increased risk of alcoholism associated with specific genotypes or haplotypes. Our results suggest that the rs356219/356221 G-A haplotype may decrease the chance of having an alcohol misuse phenotype. Conclusion: These findings suggest that alcohol misuse may alter the expression of the individual α-synuclein splice variants differently in human brain. There was no evidence of an effect of sequence variation on the expression of α-synuclein splice variants in this population.

Sex Differences in the Expression of the α5 Subunit of the GABAA Receptor in Alcoholics with and without Cirrhosis of the Liver

“…The analysis of relative expression of transcripts of interest using real‐time PCR is dependent on using a reference gene that does not differ in expression between individuals. In previous studies (Ho et al, ; Janeczek et al, ; MacKay et al, ), we have used GAPDH as a reference gene. Accordingly, the expression of GAPDH was measured in each sample by real‐time PCR.…”

“…The difference in C T values of each sample and the reference gene were expressed as the ΔC T . These values were then converted to 2 ‐ΔCT values for presentation (Ho et al, ; Janeczek et al, ; Livak and Schmittgen, ; MacKay et al, ). Data were analyzed using IBM SPSS Statistics 25 software (SPSS Inc., Chicago, IL), by performing ANOVA followed by the Tukey HSD post hoc test where appropriate.…”

Alpha-Synuclein in Alcohol Use Disorder, Connections with Parkinson’s Disease and Potential Therapeutic Role of 5’ Untranslated Region-Directed Small Molecules

“…The difference between the α-Syn 115 and α-Syn-112 transcript variants is the presence of the first 343 nucleotides of intron 4 in the 3’UTR and the absence of exon 7 in α-Syn-115. Therefore, this variant lacks the C-terminal amino acids necessary to prevent aggregation as well as a 3’UTR-containing intron 4, which has several SNPs associated with alcoholic traits [ 76 ]. The charge on this protein is five, which is higher than that of α-Syn-112 (charge of 1), making these 115 species highly aggregation prone.…”

“…The charge on this protein is five, which is higher than that of α-Syn-112 (charge of 1), making these 115 species highly aggregation prone. The full-length α-Syn 140 and truncated α-Syn 112 were significantly lower, while α-Syn-115 was higher in the brains of alcohol misusers with cirrhosis than in controls [ 76 ].…”

Ethanol (EtOH)‐Related Behaviors in α‐Synuclein Mutant Mice and Association of SNCA SNPs with Anxiety in EtOH‐Dependent Patients

“…Of particular interest are polymorphisms in the promoter region and 3′‐UTR that have the potential to influence expression of the gene (Chen et al., ; Georges et al., ). The A (rs356219) and T (rs356221) alleles have been shown to be “risk” alleles for EtOH misuse (Janeczek et al., ). The same study showed that the G (rs356219) and A (rs356221) alleles that make up the G‐A haplotype are both “protective” alleles, and the frequencies of both these alleles were lower in those abusing EtOH.…”