Wang Yuye, Qiu Luying, Jiang Wenjuan, Chen Meilin, He Zhiyi, Wang Yanzhe, Deng Shumin
Department of Neurology, China-Japan Friendship Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100029, China; Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
J Stroke Cerebrovasc Dis. 2023 Apr;32(4):106998. doi: 10.1016/j.jstrokecerebrovasdis.2023.106998. Epub 2023 Feb 11.
Let-7 family members serve as crucial regulatory molecules in the pathogenesis of ischemic stroke. We predicted that genetic variations in the let-7 family's promoters may be linked to the risk of ischemic stroke. The connection of rs10877887 and rs13293512 in the let-7 family promoters with liability to ischemic stroke was explored in this study.
Clinical data and peripheral blood samples were collected from 914 ischemic stroke patients and 836 controls in this case-control study. All statistical analyses were carried out using SPSS.
Our analysis results reveal that the rs10877887 TC+CC genotype in the dominant model is associated with a lower risk of ischemic stroke than the TT genotype. Individuals with heterozygous TC or homozygous CC genotypes in the male population showed higher odds of ischemic stroke than those with the wild TT genotype in rs13293512 analysis. Furthermore, there existed a multiplicative interaction between the rs10877887 C allele and the rs13293512 T allele. In the presence of the rs13293512 T allele, the effect of the rs10877887 C allele on ischemic stroke risk was increased. Similarly, in the presence of the rs10877887 C allele, the outcome of the rs13293512 T allele on ischemic stroke risk was elevated. In addition, the rs13293512 CC genotype seemed to lead to an earlier onset of ischemic stroke.
Our findings indicated that these two SNPs might have a joint role in IS and could potentially act as risk markers. Detecting let-7 promoter polymorphisms could raise awareness of the risk of IS, which directed individuals with risk alleles to have regular checks at an appropriate frequency to avoid developing the disease.
Let-7家族成员在缺血性脑卒中发病机制中作为关键调控分子。我们预测Let-7家族启动子的基因变异可能与缺血性脑卒中风险相关。本研究探讨了Let-7家族启动子中rs10877887和rs13293512与缺血性脑卒中易感性的关联。
在这项病例对照研究中,收集了914例缺血性脑卒中患者和836例对照的临床资料及外周血样本。所有统计分析均使用SPSS进行。
我们的分析结果显示,显性模型中rs10877887的TC + CC基因型与缺血性脑卒中风险低于TT基因型相关。在rs13293512分析中,男性人群中杂合子TC或纯合子CC基因型个体发生缺血性脑卒中的几率高于野生TT基因型个体。此外,rs10877887的C等位基因与rs13293512的T等位基因之间存在相乘交互作用。在存在rs13293512的T等位基因时,rs10877887的C等位基因对缺血性脑卒中风险的影响增加。同样,在存在rs10877887的C等位基因时,rs13293512的T等位基因对缺血性脑卒中风险的影响增强。此外,rs13293512的CC基因型似乎导致缺血性脑卒中发病更早。
我们的研究结果表明,这两个单核苷酸多态性可能在缺血性脑卒中中起联合作用,并有可能作为风险标志物。检测Let-7启动子多态性可提高对缺血性脑卒中风险的认识,指导携带风险等位基因的个体以适当频率进行定期检查,以避免发病。