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Two Novel SNPs in the PLCL2 Gene Associated with Large Artery Atherosclerotic Stroke Identified by Fine-Mapping.
Journal of Molecular Neuroscience ( IF 2.8 ) Pub Date : 2020-01-22 , DOI: 10.1007/s12031-019-01436-3
Xiaoya Huang 1 , Zhenguo Zhu 2 , Yanyan Chen 2 , Jia Li 2 , Niange Xia 2 , Siyan Chen 2 , Wujun Geng 3 , Zusen Ye 2
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A genome-wide association study (GWAS) reported that the single nucleotide polymorphism (SNP) rs4618210 in the PLCL2 gene is related to myocardial infarction (MI) in the Japanese population, but no study has examined the correlation of PLCL2 with ischemic stroke (IS). The present study was designed to investigate whether the genetic variation in PLCL2 is associated with large artery atherosclerotic (LAA) stroke in a Han Chinese population. Tagging SNPs (tSNPs) of the PLCL2 gene were determined by a fine-mapping strategy and were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 669 LAA stroke patients and 668 healthy controls. A logistic regression model was used to analyze the associations between genetic variation at PLCL2 and the risk of LAA stroke. Two SNPs were significantly associated with the risk of LAA stroke after adjusting for potential confounders: for rs4685423, the AA genotype and CA genotype decreased the risk of LAA stroke compared with the CC genotype (multivariate-adjusted, P = 0.001); for rs4618210, the AA genotype and GA genotype decreased the risk of LAA stroke compared with the GG genotype (multivariate-adjusted, P = 0.007). In addition, haplotype analysis indicated that compared with haplotype TTT, haplotype TAT decreased the risk of LAA stroke in block 2 (adjusted OR, 0.706; 95% CI, 0.550–0.907; P = 0.006). The analysis of SNP–SNP interactions showed that rs4685423 was the most influential contributor to LAA stroke risk. SNPs rs4685423 and rs4618210 in the PLCL2 gene may be related to the risk of LAA stroke in Han Chinese.

中文翻译:

PLCL2基因中的两个新的SNP与精细映射确定的大动脉粥样硬化性中风相关。

全基因组关联研究(GWAS)报告说,PLCL2基因中的单核苷酸多态性(SNP)rs4618210与日本人群的心肌梗死(MI)有关,但尚无研究检查PLCL2与缺血性卒中(IS)的相关性)。本研究旨在调查PLCL2的遗传变异是否与汉族人群中的大动脉粥样硬化(LAA)中风有关。所述的标签SNP(tSNPs)PLCL2该基因通过精细定位策略确定,并通过改良的多重连接检测反应(iMLDR)技术对669名LAA中风患者和668名健康对照进行基因分型。使用逻辑回归模型分析PLCL2的遗传变异与LAA中风风险之间的关联。校正潜在的混杂因素后,有两个SNP与LAA中风的风险显着相关:对于rs4685423,与CC基因型相比,AA基因型和CA基因型降低了LAA中风的风险(多元校正,P = 0.001)。对于rs4618210,与GG基因型相比,AA基因型和GA基因型降低了LAA中风的风险(多因素调整,P= 0.007)。此外,单倍型分析表明,与单倍型TTT相比,单倍型TAT降低了第2区的LAA中风的风险(校正OR,0.706; 95%CI,0.550-0.907;P = 0.006)。对SNP–SNP相互作用的分析表明,rs4685423是LAA中风风险的最有影响力的因素。PLCL2基因中的SNP rs4685423和rs4618210可能与汉族人发生LAA的风险有关。
更新日期:2020-01-22
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