Department of Neurology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.
Department of Neurology, Beijing Xuanwu Hospital, Chinese Human Genetic Center, Beijing, China.
Neurosci Lett. 2014 Jan 24;559:158-62. doi: 10.1016/j.neulet.2013.11.038. Epub 2013 Dec 1.
Previous studies have corroborated receptor for advanced glycation end-products (RAGE) ablation had a protective effect on nigral dopaminergic neurons in the MPTP model of Parkinson's disease (PD). Genetic variation of RAGE gene may be associated with the development of onset of sporadic PD. The present study aimed to explore the possible association of RAGE gene polymorphisms namely -374T/A,-429T/C, and G82S with PD. A total of 285 PD patients and 285 healthy-matched individuals in Chinese Han population were enrolled. Genotype analyses were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Only the -429T/C polymorphism denoted a significant difference between PD patients and controls (P=0.015) of the three examined single nucleotide polymorphisms (SNPs). Our data also revealed that -429C allele carriers seem to have a decreased risk of PD (OR=0.617, P=0.007). Moreover, there were significant differences in genotype distribution in female PD group and its healthy-matched control subgroup (P=0.014), as well as between late-onset PD (LOPD) and the controls subgroup (P=0.016). However, for -374T/A and 82GS polymorphisms, there was no significant difference in the genotype and allele frequencies between PD patients and the controls, as well as gender- and age-related differences. Our present findings indicate that the RAGE -429T/C polymorphism may be associated with the susceptibility of PD and the CC genotype of -429T/C may be a protective factor for PD in Chinese Han population.
先前的研究证实,晚期糖基化终产物受体(RAGE)的缺失对 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型中的黑质多巴胺能神经元具有保护作用。RAGE 基因的遗传变异可能与散发性 PD 的发病有关。本研究旨在探讨 RAGE 基因多态性 -374T/A、-429T/C 和 G82S 与 PD 之间的可能关联。共纳入了 285 例 PD 患者和 285 例中国汉族健康对照者。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)进行基因型分析。在三个被检测的单核苷酸多态性(SNP)中,只有 -429T/C 多态性在 PD 患者和对照组之间存在显著差异(P=0.015)。我们的数据还表明,-429C 等位基因携带者似乎患 PD 的风险降低(OR=0.617,P=0.007)。此外,在女性 PD 组及其健康对照组亚组(P=0.014)以及迟发性 PD(LOPD)与对照组亚组(P=0.016)中,基因型分布存在显著差异。然而,对于 -374T/A 和 82GS 多态性,PD 患者和对照组之间的基因型和等位基因频率以及性别和年龄相关差异均无显著差异。本研究结果表明,RAGE -429T/C 多态性可能与 PD 的易感性有关,-429T/C 的 CC 基因型可能是中国汉族人群 PD 的保护因素。