Objective To investigate clinical significance of Homer expression in peripheral blood leukocytes of patients with ischemic stroke (IS).Methods It was a retrospecive study.The gene expression levels of Homer were measured by RT-qPCR.266 patientscollected in Zhongnan Hospital from September 2015 to June 2016were divided into 5 groups:large-artery atherosclerosis (LAA,100 cases),cardioembolism (CE,42 cases),small vessel occlusion (SVO,68 cases),stroke of other demonstrated etiology (SOE,23 cases) and stroke of undemonstrated etiology (SUE,33 cases).Meanwhile,age and sex matched 126 healthy controls were also collected.IS diagnostic criteria for cerebral infarctionwas in accordance with the guideline for acute ischemic stroke in China in 2010.The levels of Homers in subgroups were compared by Oneway ANOVA.The area under curve (AUC) and 95％ confidence interval (CI) were calculated using ROC analyses.The odds ratio (OR) and 95％ CI were calculated using the multivariate logistic regression analyses.Results The levels of Homer1 [2.01 ± 0.15] and Homer2 [1.81 ± 0.31] in LAA patients were significantly higher than othergroups [Homer1 CE:2.40 ± 0.34;SVO:2.38 ± 0.35;SOE:2.36 + 0.33;SUE:2.40 ± 0.30;control group:2.35 ± 0.28;Homer2 CE:2.09 ± 0.38;SVO:2.08 ± 0.30;SOE:2.09 ± 0.41;SUE:2.10 ± 0.34;control group:2.12 ± 0.31] (Homer1 CE:t =9.353,P＜0.001;SVO:t =9.258,P＜0.001;SOE:t =5.396,P＜0.001;SUE:t=9.644,P＜0.001;control group:t =11.882,P＜0.001;Homer2 CE:t =4.725,P＜0.001;SVO:t =5.545,P＜0.001;SOE:t=3.640,P ＜ 0.001;SUE:t =4.669,P ＜ 0.001);There was no significant difference in the expression of Homer1 (F =0.940,P =0.441) and Homer2 (F =0.336,P =0.854) between non-LAA groupsand healthy controls.There was no significant difference in the expression of Homer3among the groups (F =0.641,P =0.669).Multinomial logistic regression analyses revealed that,higher Homerl (adjusted OR =8.62,95％ CI:4.13-18.00,P＜0.001) and Homer2 (adjusted OR=2.42,95％ CI:1.75-3.36,P ＜ 0.001) levels showed significant associations with increased odds of having LAA stroke,compared with the controls.ROC curves showed that the AUC of the combination of Homer1 and Homer2 for differentiating LAA and controls was 0.896 (95％ CI:0.862-0.929,P ＜0.001) and the AUCfor differentiating LAAand non-LAA was 0.847 (95％ CI:0.800-0.894,P ＜ 0.001).Conclusion The expression of Homer1 and Homer2 in peripheral blood leukocytes could be used as novel biomarkers for LAA stroke.