Department of Neurology, Henan Provincial People's Hospital, School of Clinical Medicine, Henan University, 7 Weiwu Road, Zhengzhou, Henan Province, 450003, PR China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 1 Jian She East Road, Zhengzhou, Henan Province, 450007, PR China.
Neurosci Lett. 2019 Jul 27;706:146-150. doi: 10.1016/j.neulet.2019.05.026. Epub 2019 May 15.
Single-nucleotide polymorphisms (SNPs) in the SNCA gene encoding alpha-synuclein have been shown to affect the PD phenotype. However, whether such polymorphisms can influence risk of dementia in PD remains unclear.
To investigate possible associations between SNCA gene polymorphisms and dementia in patients with PD.
A consecutive series of 291 PD patients with dementia (n = 45, 15.5%) or without it (n = 246, 84.5%) were genotyped at four SNPs in the SNCA gene. As controls, 615 healthy Han Chinese were also genotyped.
Three SNPs (rs11931074, rs7684318 and rs356219) were in strong linkage disequilibrium. The GG genotype at rs11931074 significantly reduced risk of PD (p = 0.023), but it significantly increased risk of dementia after PD onset (p = 0.015) based on the recessive genetic model. Logistic regression identified the following risk factors for dementia among patients with PD: age ≥65 years (odds ratio [OR] 2.69, 95% confidence interval [CI] 1.25-5.77, p = 0.011), education ≤6 years (OR 4.66, 95% CI 2.21-9.83, p < 0.001), part III score on the Unified Parkinson's Disease Rating Scale ≥40 (OR 5.01, 95% CI 2.40-10.45, p < 0.001), and GG genotype at rs11931074 (OR 2.81, 95% CI 1.16-6.83, p = 0.022).
PD patients carrying the protective GG genotype at SNCA rs11931074 may be at significantly higher risk of dementia than patients with other genotypes. Our results support the view that SNCA polymorphisms can have opposite effects on preclinical and clinical PD.
编码α-突触核蛋白的 SNCA 基因中的单核苷酸多态性 (SNP) 已被证明会影响 PD 表型。 然而，这些多态性是否会影响 PD 患者痴呆的风险尚不清楚。
研究 SNCA 基因多态性与 PD 患者痴呆之间的可能关联。
对 291 名患有痴呆症的 PD 患者（n=45，15.5%）或无痴呆症的 PD 患者（n=246，84.5%）进行连续系列研究，对 SNCA 基因中的四个 SNP 进行基因分型。 作为对照，对 615 名健康汉族人也进行了基因分型。
三个 SNP（rs11931074、rs7684318 和 rs356219）处于高度连锁不平衡状态。基于隐性遗传模型，rs11931074 的 GG 基因型显著降低 PD 风险（p=0.023），但显著增加 PD 发病后的痴呆风险（p=0.015）。 逻辑回归确定了 PD 患者痴呆的以下危险因素：年龄≥65 岁（比值比 [OR] 2.69，95%置信区间 [CI] 1.25-5.77，p=0.011）、教育程度≤6 年（OR 4.66，95% CI 2.21-9.83，p<0.001）、统一帕金森病评定量表第 III 部分评分≥40 分（OR 5.01，95% CI 2.40-10.45，p<0.001）和 rs11931074 的 GG 基因型（OR 2.81，95% CI 1.16-6.83，p=0.022）。
携带 SNCA rs11931074 保护性 GG 基因型的 PD 患者发生痴呆的风险可能明显高于其他基因型的患者。 我们的结果支持这样一种观点，即 SNCA 多态性对临床前和临床 PD 可能具有相反的影响。
