5’UTR Variant rs6017916 Regulates SRC Expression and Contributes to the Susceptibility to Ischemic Stroke in the Chinese Han Population

Previous studies reported that the SRC protein was involved in a variety of pathological mechanisms related to ischemic stroke (IS). In this study, we conducted a genetic association study between rs6017916 within the 5’UTR region of SRC gene and IS susceptibility. A total of 533 IS patients and 531 healthy controls were recruited to participate in the current study. The sequenom MassARRAY technology platform was used for genotyping. The quantitative polymerase chain reaction (qPCR) was conducted to detect SRC mRNA expression. The dual luciferase reporter system was used to verify the regulation of rs6017916 on SRC mRNA expression. Results showed that SRC mRNA expression was significantly increased in IS patients than that in controls (P<0.001). Receiver operating characteristic curve (ROC) analysis demonstrated that the signature of SRC mRNA expression differentiated between controls and IS patients with an area under the curve (AUC) of 0.935 corresponding to a specificity of 0.820 and sensitivity of 0.920. Genetic association analysis showed that rs6017916 was significantly associated with IS susceptibility under multiple genetic models, including additive [OR (95% CI)=0.76 (0.60,0.96), Padj=0.019] and dominant [OR (95% CI)=0.75(0.58,0.98), Padj=0.031]. In addition, the dual luciferase reporter system showed that the minor allele C of rs6017916 inhibited luciferase activity compared with the major allele A. In summary, we report that SRC mRNA expression was significantly increased in IS patients and was a potential diagnostic biomarker. Moreover, the 5’UTR variant rs6017916 of SRC was significantly associated with IS susceptibility. And rs6017916 might affect the pathological process of IS by regulating SRC expression.