Background: Early cognitive impairment after transient ischemic stroke (TIA)/mild ischemic stroke (MIS) is common but easily overlooked. It has been demonstrated that DNA methylation plays a significant role in cognitive impairment and ischemic stroke. Furthermore, it has been reported that the RIN3  gene influences transportation of the amyloid β-protein. However, to our knowledge, there has been no research related to correlations between RIN3  methylation and early-onset cognitive impairment after TIA/MIS. Therefore, this study aimed to investigate this relationship in TIA/MIS patients.
Methods: This study include 28 control subjects and 84 patients with TIA/MIS who were evaluated within 7 days of TIA/MIS onset using four single-domain cognitive scales. In addition, DNA methylation of whole blood was tested. RIN3  methylation was compared between TIA/MIS and control groups and between TIA/MIS patients with early cognitive impairment and those without early cognitive impairment. Clinical variables and RIN3  methylation sites with statistical differences were then used to construct a predictive model.
Results: Hypomethylation of the RIN3  gene was observed in the whole blood of TIA/MIS patients relative to healthy controls. Furthermore, patients with early cognitive impairment after TIA/MIS had hypomethylation of RIN3  relative to those without early cognitive impairment.
Conclusion: RIN3  methylation is strongly associated with TIA/MIS and TIA/MIS with early cognitive impairment. It is possible to influence the disease process by methylation via appropriate lifestyle and clinical interventions, and methylation of RIN3  gene sites may predict the occurrence of TIA/MIS with early cognitive impairment.
Keywords: amyloid β-protein, cognitive impairment, hypomethylation, ischemic stroke, transportation