Chen YongPing, Cao Bei, Yang Jing, Wei QianQian, Ou Ru Wei, Zhao Bi, Song Wei, Guo XiaoYan, Shang HuiFang
Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
J Neurol. 2015 Nov;262(11):2478-83. doi: 10.1007/s00415-015-7870-9. Epub 2015 Aug 8.
Whether polymorphisms rs11856808 and rs9652490 of the Leucine-rich repeat and Ig domain containing, Nogo receptor-interacting protein-1 (LINGO1) gene, as well as rs10968280, rs13362909 and rs7033345 of the LINGO2 gene, increase the risk for Parkinson's disease (PD) is controversial. Considering the overlap of the clinical and pathological characteristics among PD and multiple system atrophy (MSA), we explored the associations between these five polymorphisms and PD and MSA in a Chinese population. A total of 1055 PD patients, 320 MSA patients, and 810 healthy controls (HCs) were genotyped for these five polymorphisms in LINGO1 and LINGO 2 using Sequenom iPLEX Assay technology. Moreover, after combining our results with available published data, a meta-analysis was conducted to investigate the associations between LINGO 1 rs11856808 and rs9652490 and the risk of PD. The frequency of the minor alleles "T" of LINGO1 rs11856808 was significantly lower in PD than that in HCs (p = 0.011, OR 0.89, 95 % CI 0.81-0.97), but not in MSA. Moreover, there were no significant differences in the minor allele frequency distributions of the other four polymorphisms between PD and HCs, and between MSA and HCs. The meta-analysis showed a lack of association of rs9652490 and PD, regardless of the genetic model or ethnic origin. However, the rs11856808 allele decreased the risk of PD in patients of Asian origin in a dominant genetic model. Our findings suggest that rs11856808 plays a protective role by decreasing the risk for PD, but not for MSA, in Asian population, the other four polymorphisms do not contribute to the risk for PD and MSA.
富含亮氨酸重复序列和免疫球蛋白结构域的Nogo受体相互作用蛋白1(LINGO1)基因的多态性rs11856808和rs9652490,以及LINGO2基因的rs10968280、rs13362909和rs7033345是否会增加帕金森病(PD)的风险仍存在争议。考虑到PD与多系统萎缩(MSA)在临床和病理特征上的重叠,我们在中国人群中探讨了这五种多态性与PD和MSA之间的关联。使用Sequenom iPLEX检测技术对1055例PD患者、320例MSA患者和810例健康对照(HC)进行了LINGO1和LINGO 2这五种多态性的基因分型。此外,将我们的结果与已发表的可用数据相结合后,进行了一项荟萃分析,以研究LINGO 1 rs11856808和rs9652490与PD风险之间的关联。LINGO1 rs11856808的次要等位基因“T”在PD患者中的频率显著低于HC(p = 0.011,OR 0.89,95%CI 0.81 - 0.97),但在MSA患者中并非如此。此外,PD与HC之间以及MSA与HC之间,其他四种多态性的次要等位基因频率分布没有显著差异。荟萃分析表明,无论遗传模型或种族来源如何,rs9652490与PD均无关联。然而,在显性遗传模型中,rs11856808等位基因降低了亚洲裔患者患PD的风险。我们的研究结果表明,在亚洲人群中,rs11856808通过降低患PD的风险发挥保护作用,但对MSA无此作用,其他四种多态性与PD和MSA的风险无关。