Chemokine Gene Polymorphisms Influence Mortality in Patients with Acute Ischemic Cerebrovascular Events in China

Abstract

Abstract Background: Chemokines are major mediators of leukocyte trafficking into the sites of the inflammatoryresponse and have received more attention for their roles in ischemic cerebrovascular events. Our study aimed to evaluate the relationships between single nucleotide polymorphisms (SNP) of chemokine genes and mortalityin patients with acute ischemic cerebrovascular events in China. Methods: We derived data from the Third China National Stroke Registry (CNSR-Ⅲ). Atotal of 10,241 patients had complete whole-genome sequencing information and formed the genetic subgroup of CNSR-Ⅲ. The Cox proportional hazards regression model was used to investigate the associations ofSNPs with death. The Spearman rank correlation was used to evaluate the associations of SNPs with leukocyte counts. We performed the mediation analysis to estimate whether leukocytes mediate the relationships of SNPs with death. Furthermore, we constructed a chemokine gene polymorphisms risk score for death. Results: A total of 15 SNPs of chemokine genes were found to be associated with death. CCL1 rs2282691, CCL1 rs2282692 and CCL27 rs2812365 were related to reduced risk of death, and the other 12 SNPs exhibited correlations with elevated risk. CCL27rs2812365 was related to counts of leukocyte, neutrophil and monocyte. CCL2rs2857657 was correlated with eosinophil count. The mediation analysis, however, could not suggest that leukocytes account for the relationships between SNPs and death. Patients with higher risk scores were found to have a higher risk of death. Conclusion: The SNPs of chemokine genes were associated with the risk of death in patients with acute ischemic cerebrovascular events in China.