Institute of Neurological Sciences, Cosenza, Italy.
Am J Med Genet B Neuropsychiatr Genet. 2011 Jan;156B(1):104-7. doi: 10.1002/ajmg.b.31129. Epub 2010 Nov 2.
The major component of Lewy Bodies (LB), the pathological hallmark of Parkinson's disease (PD) is α-synuclein, most prominently phosphorylated at serine 129. G-protein coupled receptor kinase 5 (GRK5) has been reported to phosphorylate α-synuclein in vitro, enhancing the α-synuclein toxicity to dopaminergic neurons in Drosophila model. Moreover, GRK5 was found in LBs from brain of PD patients. A genetic association study performed in the Japanese population revealed haplotypic association of the GRK5 gene with susceptibility to sporadic PD. We aimed at investigating whether four polymorphisms within the GRK5 gene (rs871196, rs2420616, rs7069375, rs4752293) could represent a risk factor for sporadic PD in Southern Italy. We genotyped 446 patients with PD and 450 controls for these markers and did not find any significant association with the disease at allelic, genotypic and haplotypic level. Our results indicate that the GRK5 gene does not confer risk to sporadic PD in our sample from Southern Italy.
路易体（LB）的主要成分是帕金森病（PD）的病理学标志物α-突触核蛋白，最突出的是丝氨酸 129 磷酸化。已报道 G 蛋白偶联受体激酶 5（GRK5）在体外磷酸化α-突触核蛋白，增强了果蝇模型中多巴胺能神经元的α-突触核蛋白毒性。此外，在 PD 患者的脑 LB 中发现了 GRK5。在日本人群中进行的一项遗传关联研究表明，GRK5 基因的单倍型与散发性 PD 的易感性相关。我们旨在研究 GRK5 基因内的四个多态性（rs871196、rs2420616、rs7069375、rs4752293）是否可以作为意大利南部散发性 PD 的危险因素。我们对 446 名 PD 患者和 450 名对照进行了这些标记物的基因分型，在等位基因、基因型和单倍型水平上均未发现与疾病有任何显著关联。我们的结果表明，GRK5 基因在我们来自意大利南部的样本中不会导致散发性 PD 的风险。
