Janeczek Paulina, MacKay Rachel K, Lea Rodney A, Dodd Peter R, Lewohl Joanne M
Griffith Health Institute, School of Medical Sciences, Griffith University, Australia.
Addict Biol. 2014 May;19(3):509-15. doi: 10.1111/j.1369-1600.2012.00495.x. Epub 2012 Sep 13.
α-Synuclein has recently been implicated in the pathophysiology of alcohol abuse due to its role in dopaminergic neurotransmission. In these studies, genetic variability in the α-synuclein gene influences its expression which may contribute to susceptibility to chronic alcohol abuse. Real-time PCR was used to quantify α-synuclein mRNA expression in autopsy samples of human dorsolateral prefrontal cortex. Because of the association between length of the α-synuclein-repeat 1 microsatellite marker and expression levels of the gene, this marker was genotyped in a Caucasian sample of 126 controls and 117 alcoholics using capillary gel electrophoresis. The allele and genotype frequencies of α-synuclein-repeat 1 marker differed significantly between alcoholics and controls. Alcoholics had greater frequencies of the shortest allele found (267 bp). The shortest allele of the α-synuclein-repeat 1 marker was associated with decreased expression of α-synuclein in prefrontal cortex. Individuals with at least one copy of the 267 bp allele were more likely to exhibit an alcohol abuse phenotype. These results suggest that individuals with the 267 bp allele may be at increased risk of developing alcoholism and that genetic variation at the α-synuclein-repeat 1 locus may influence α-synuclein expression in the prefrontal cortex.
由于α-突触核蛋白在多巴胺能神经传递中的作用，它最近被认为与酒精滥用的病理生理学有关。在这些研究中，α-突触核蛋白基因的遗传变异性影响其表达，这可能导致对慢性酒精滥用的易感性。使用实时聚合酶链反应（PCR）来定量人类背外侧前额叶皮质尸检样本中α-突触核蛋白信使核糖核酸（mRNA）的表达。由于α-突触核蛋白重复序列1微卫星标记的长度与该基因的表达水平之间存在关联，因此使用毛细管凝胶电泳对126名对照者和117名酗酒者的高加索样本中的该标记进行基因分型。α-突触核蛋白重复序列1标记的等位基因和基因型频率在酗酒者和对照者之间存在显著差异。酗酒者中发现的最短等位基因（267bp）的频率更高。α-突触核蛋白重复序列1标记的最短等位基因与前额叶皮质中α-突触核蛋白表达的降低有关。至少有一个267bp等位基因拷贝的个体更有可能表现出酒精滥用表型。这些结果表明，具有267bp等位基因的个体可能患酒精中毒的风险增加，并且α-突触核蛋白重复序列1位点的基因变异可能影响前额叶皮质中α-突触核蛋白的表达。
