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Association between microRNA binding site polymorphisms in immunoinflammatory genes and recurrence risk of ischemic stroke

Zhu, Ruixia, Zhao, Yating, Xiao, Tongling, Wang, Qianwen, Liu, Xu
Genomics 2019
CXCR2 receptor, Toll-like receptor 4, binding sites, biomarkers, genes, genetic markers, genotype, genotyping, human diseases, microRNA, models, patients, prediction, prognosis, regression analysis, risk, stroke, therapeutics
MicroRNA binding site polymorphisms in immunoinflammatory genes have been implicated as candidate biomarkers for prediction of complex human diseases. However, the roles of microRNA binding site polymorphisms in stroke onset and prognosis remain unclear. Thus, for the first time, five potential functional polymorphisms in immunoinflammatory genes (CXCR2 rs1126579, TLR4 rs11536889, ADIPOR2 rs12342, MMP-2 rs7201 and MMP-9 rs1056628) were genotyped in 657 patients with ischemic stroke. These five polymorphisms were not related with age onset of ischemic stroke. However, we found that ADIPOR2 rs12342 was significantly associated with a decreased recurrence risk, especially for the patients with small-vessel disease. Moreover, by using multivariate Cox regression, the variant genotype GG/GA of rs12342 was observed as an independent protective factor for stroke recurrence, even after Bonferroni correction. In addition, after the addition of rs12342 in the model with clinical factors, the new model showed the improved discriminatory ability to predict stroke recurrence. In short, our results suggested that ADIPOR2 rs12342 may be a novel genetic biomarker and therapeutic target for ischemic stroke recurrence. Further studies are required to replicate our findings and clarify the potential biological mechanism.