A Comprehensive Analysis of the Association Between SNCA Polymorphisms and the Risk of Parkinson's Disease.
A Comprehensive Analysis of the Association Between SNCA Polymorphisms and the Risk of Parkinson's Disease.
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SNCA多态性与帕金森病风险关联性综合分析
DOI：
10.3389/fnmol.2018.00391
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发表时间：
2018
影响因子：
4.8
通讯作者：
Tang B
中科院分区：
文献类型：
--
作者：
Zhang Y;Shu L;Sun Q;Pan H;Guo J;Tang B
背景：许多研究报道了突触核蛋白α（SNCA）多态性与帕金森病（PD）风险之间的相关性。然而，结果是不一致的。我们对SNCA单核苷酸多态性（SNPs）与PD风险之间的关系进行了一项综合性荟萃分析，包括总体人群和按种族划分的亚群。方法：根据我们的方案进行标准荟萃分析，临界点为p < 0.05。为了找到最相关的SNCA SNP，我们在基于等位基因模型的分析中使用了p < 1 × 10−5的临界点。在按种族进行的亚组分析中，我们将总体人群分为五个种族组。我们使用显性和隐性模型对最相关的SNP进行了进一步分析，以确定每个SNP的杂合子和纯合子的贡献。结果：在我们的综合荟萃分析中，纳入了来自36篇文章的24，075例病例和22，877例对照。我们在荟萃分析中纳入了16个变异，发现12个具有统计学意义的变异，p < 0.05。在使用p < 1 × 10 - 5的临界值缩小变异范围后，在总体人群中，7个SNP增加了PD的风险（rs 2736990、rs356220、rs356165、rs 181489、rs356219、rs 11931074和rs 2737029，优势比[OR]为1.22-1.38）和一个SNP降低了风险（rs356186，OR为0.77）。在东亚组中，rs 2736990和rs 11931074增加了风险（OR为1.22-1.34）。在欧洲组中，5个SNP增加了风险（rs356219，rs 181489，rs 2737029，rs356165和rs 11931074，OR为1.26-1.37），而1个SNP降低了风险（rs356186，OR为0.77）。杂合子和纯合子的贡献不同，这取决于变异。结论：本研究共发现8个SNCA单核苷酸多态性与PD风险相关，且在种族间存在明显差异。在整个人群中，7个SNP增加了PD的风险，1个SNP降低了风险。在东亚组中，rs 2736990和rs 11931074增加了风险。在欧洲组中，rs356219、rs 181489、rs 2737029、rs356165和rs 11931074增加了风险，而rs356186降低了风险。在我们的分析中具有最高OR和等位基因频率的变体在进行遗传筛查时应被优先考虑。
Background: Various studies have reported associations between synuclein alpha (SNCA) polymorphisms and Parkinson's disease (PD) risk. However, the results are inconsistent. We conducted a comprehensive meta-analysis of the associations between SNCA single-nucleotide polymorphisms (SNPs) and PD risk in overall populations and subpopulations by ethnicity. Methods: Standard meta-analysis was conducted according to our protocol with a cutoff point of p < 0.05. To find the most relevant SNCA SNPs, we used a cutoff point of p < 1 × 10−5 in an analysis based on the allele model. In the subgroup analysis by ethnicity, we divided the overall populations into five ethnic groups. We conducted further analysis on the most relevant SNPs using dominant and recessive models to identify the contributions of heterozygotes and homozygotes regarding each SNP. Results: In our comprehensive meta-analysis, 24,075 cases and 22,877 controls from 36 articles were included. We included 16 variants in the meta-analysis and found 12 statistically significant variants with p < 0.05. After narrowing down the variants using the p < 1 × 10−5 cutoff, in overall populations, seven SNPs increased the risk of PD (rs2736990, rs356220, rs356165, rs181489, rs356219, rs11931074, and rs2737029, with odds ratios [ORs] of 1.22–1.38) and one SNP decreased the risk (rs356186, with an OR of 0.77). In the East Asian group, rs2736990 and rs11931074 increased the risk (with ORs of 1.22–1.34). In the European group, five SNPs increased the risk (rs356219, rs181489, rs2737029, rs356165, and rs11931074, with ORs of 1.26–1.37) while one SNP decreased the risk (rs356186, with an OR of 0.77). The heterozygotes and homozygotes contributed differently depending on the variant. Conclusions: In summary, we found eight SNCA SNPs associated with PD risk, which had obvious differences between ethnicities. Seven SNPs increased the risk of PD and one SNP decreased the risk in the overall populations. In the East Asian group, rs2736990 and rs11931074 increased the risk. In the European group, rs356219, rs181489, rs2737029, rs356165, and rs11931074 increased the risk while rs356186 decreased the risk. Variants with the highest ORs and allele frequencies in our analysis should be given priority when carrying out genetic screening.
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影响因子：
11.2
作者：
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通讯作者：
Sawcer, Stephen J.
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通讯作者：
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