Association analyses of variants of SIPA1L2, MIR4697, GCH1, VPS13C, and DDRGK1 with Parkinson's disease in East Asians
Association analyses of variants of SIPA1L2, MIR4697, GCH1, VPS13C, and DDRGK1 with Parkinson's disease in East Asians
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SIPA1L2、MIR4697、GCH1、VPS13C 和 DDRGK1 变异与东亚人帕金森病的关联分析
DOI：
10.1016/j.neurobiolaging.2018.03.005
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发表时间：
2018-08-01
影响因子：
4.2
通讯作者：
Zhu, Jian-Hong
中科院分区：
文献类型：
--
作者：
Zou, Ming;Li, Rui;Zhu, Jian-Hong
最近一项来自欧洲的大规模全基因组关联数据荟萃分析和一项重复研究确定了6个新的帕金森病（PD）风险位点，包括rs10797576/SIPA1L2、rs117896735/INPP5F、rs329648/MIR4697、rs11158026/GCH1、rs2414739/VPS13C和rs8118008/DDRGK1。然而，这些新的基因位点是否与亚洲人群的帕金森病有关仍然是一个谜。INPP5F在亚洲人中是无多态性的。本研究旨在了解另外5个新基因座在579例散发性PD患者和642例对照人群中的作用。SIPA1L2变异（p = 0.001）和VPS13C变异（p = 0.007）与PD显著相关，其中T（奇数比[OR] = 1.484, 95%可信区间[CI] 1.186-1.858）和A （OR = 1.362, 95%可信区间[CI] 1.087 -1.707）等位基因分别为危险等位基因。SIPA1L2和VPS13C变异的基因型分布在患者和对照组之间也存在差异（p = 0.002和p = 0.023）。相比之下，MIR4697、GCH1和DDRGK1的变异在等位基因或基因型频率上均未发现与PD有显著关联。值得注意的是，随后的东亚研究荟萃分析表明GCH1变异与PD相关（p = 0.04, OR 1.08, 95% CI 1.00-1.16），而其他结果与我们的队列一致。总之，我们的研究和荟萃分析表明，SIPA1L2和VPS13C的变异，可能是GCH1，而不是MIR4697和DDRGK1，与东亚人的PD易感性相关。(C) 2018爱思唯尔公司版权所有。
A recent large-scale European-originated genome-wide association data meta-analysis followed by a replication study identified 6 new risk loci for Parkinson's disease (PD), which include rs10797576/SIPA1L2, rs117896735/INPP5F, rs329648/MIR4697, rs11158026/GCH1, rs2414739/VPS13C, and rs8118008/DDRGK1. However, whether these new loci are associated with PD in Asian populations remain elusive. The INPP5F is nonpolymorphic in Asians. The present study aimed to understand the effects of the other 5 new loci in a Han Chinese population comprising 579 sporadic PD patients and 642 controls. Significant associations with PD were observed in the variants of SIPA1L2 (p = 0.001) and VPS13C (p = 0.007), where the T (odd ratio [OR] = 1.484, 95% confidence interval [CI] 1.186-1.858) and A (OR = 1.362, 95% CI 1.087 -1.707) alleles serve as the risk alleles, respectively. The genotype distributions in the SIPA1L2 and VPS13C variants were also different between the patients and controls (p = 0.002 and p = 0.023, respectively). In contrast, no significant association with PD was found in the variants of MIR4697, GCH1, and DDRGK1 either in allele or genotype frequencies. Noteworthy, a followed meta-analysis of East Asian studies suggested an association of the GCH1 variant with PD (p = 0.04, OR 1.08, 95% CI 1.00-1.16), while the other results are in line with those of our cohort. In conclusion, our study together with meta-analyses demonstrates that the variants of SIPA1L2 and VPS13C, potentially GCH1, but not of MIR4697 and DDRGK1, are associated with PD susceptibility in East Asians. (C) 2018 Elsevier Inc. All rights reserved.