Chang Kuo-Hsuan, Wu Yih-Ru, Chen Yi-Chun, Fung Hon-Chung, Lee-Chen Guey-Jen, Chen Chiung-Mei
From the Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine (K-HC, Y-RW, Y-CC, H-CF, C-MC); and Department of Life Science, National Taiwan Normal University, Taipei, Taiwan (C-JL-C).
Medicine (Baltimore). 2015 Oct;94(41):e1690. doi: 10.1097/MD.0000000000001690.
Neuroinflammation is emerging as an important pathway involved in Parkinson's disease (PD) pathogenesis. Herein, we investigated the effect of 4 top PD-associated genetic variants in Caucasians listed on the top risk loci identified by meta-analysis of genome wide-association studies in PDGene database (http://www.pdgene.org/top_results), including serine threonine kinase 39 (STK39) rs1955337, bone marrow stromal cell antigen 1 (BST1) rs11724635, major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1) rs9275326, and signal peptide peptidase-like 2B (SPPL2B) rs62120679, by genotyping 596 Han-Chinese patients with PD and 597 age-matched control subjects. Compared with subjects with STK39 rs1955337 GG genotype, those with TT genotype had a 1.64-fold increased risk of PD (95% confidence interval: 1.13-2.39, P = 0.010). The recessive model also demonstrated an increased PD risk in TT genotype (odds ratio: 1.59, 95% confidence interval: 1.12-2.27) compared with the other genotypes (GT + GG). PD patients demonstrate a similar genotypic and allelic frequency in BST1 rs11724635, HLA-DQB1 rs9275326, and SPPL2B rs62120679 compared with controls. These findings suggested that the STK39 rs1955337 TT genotype is a risk factor for Han-Chinese patients with PD in Taiwan. The ethnic discrepancies of the other 3 genetic variants may indicate a distinct genetic background of neuroinflammation between PD patients in Han-Chinese and Caucasians.
神经炎症正成为帕金森病(PD)发病机制中的一条重要途径。在此,我们通过对596例汉族PD患者和597例年龄匹配的对照者进行基因分型,研究了PD基因数据库(http://www.pdgene.org/top_results)中全基因组关联研究荟萃分析确定的顶级风险位点上列出的4个与PD相关的顶级遗传变异在高加索人中的作用,这些变异包括丝氨酸苏氨酸激酶39(STK39)rs1955337、骨髓基质细胞抗原1(BST1)rs11724635、主要组织相容性复合体II类DQβ1(HLA - DQB1)rs9275326和信号肽肽酶样2B(SPPL2B)rs62120679。与STK39 rs1955337 GG基因型的受试者相比,TT基因型的受试者患PD的风险增加了1.64倍(95%置信区间:1.13 - 2.39,P = 0.010)。隐性模型也显示,与其他基因型(GT + GG)相比,TT基因型的PD风险增加(优势比:1.59,95%置信区间:1.12 - 2.27)。与对照组相比,PD患者在BST1 rs11724635、HLA - DQB1 rs9275326和SPPL2B rs62120679中表现出相似的基因型和等位基因频率。这些发现表明,STK39 rs1955337 TT基因型是台湾汉族PD患者的一个风险因素。其他3个遗传变异的种族差异可能表明汉族和高加索PD患者之间神经炎症的遗传背景不同。