Abstract：
The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.
摘要：
早期神经功能恶化（END）的发生率在缺血性卒中的不同亚型中有所不同。先前的研究表明PLCL2基因是动脉粥样硬化和血栓事件发生的新的易感位点。这项研究的目的是检查PLCL2可能对大动脉粥样硬化（LAA）中风中END风险的功效。通过精细作图策略鉴定标记的单核苷酸多态性(SNP)。通过SNPscan进行所选SNP的基因分型。通过二元逻辑回归评估PLCL2对LAA患者END易感性的影响。通过广义多因子降维（GMDR）评估PLCL2对END的SNP-SNP相互作用。共招募了1527名LAA卒中患者，582例患者（38%）经历了END。与没有END的参与者相比，经历END的参与者年龄更大(P=0.018)，更可能患有预先存在的糖尿病（P=0.036），活跃烟草使用者的频率更高（P=0.022），入院时NIHSS中位数更高（P<0.001）。Rs4685423被确定为END风险的预测因子：AA基因型患者的END频率低于AC或CC基因型患者（多变量调整，OR0.63；95%CI0.49-0.80；P<0.001）。SNP-SNP相互作用分析表明rs4685423对LAA患者的END风险影响最大。AA基因型患者从入院诊断到END发病的时间比CA或CC基因型患者晚得多(log-rank,P=0.005)。总之,PLCL2rs4685423SNP可能与LAA卒中患者的END风险相关.
