Objective To evaluate the associations of 16 variants in clopidogrel-relevant genes with early neurological deterioration (END) in acute ischemic stroke (AIS) patients receiving clopidogrel treatment. Methods AIS patients admitted to the Department of Neurology of three hospitals between June 2014 and January 2015 were included. The 16 variants in clopidogrel-relevant genes were examined using mass spectrometry. Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction (GMDR) methods. The primary outcome was END within the 10 days of admission. Results A total of 375 patients with AIS were included. Among the 375 patients, 95 (25.33%) patients developed END within the first 10 days of admission. Among the 16 variants, only CYP2C19*2 rs4244285 AG+AA was associated with END using single-locus analytical approach (P<0.001). GMDR analysis revealed that there was a synergistic effect of gene-gene interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPⅢa rs2317676 on risk for END (P=0.019). Cox regression analysis showed that the high-risk interactive genotype was independent predictor for END [hazard ratio=2.184, 95% confidence interval (1.472, 3.238), P=0.004]. Conclusions END is very common in patients with AIS. Interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPⅢa rs2317676 may confer a higher risk for END. It may be very important to modify clopidogrel therapy for the patients carrying the high-risk interactive genotype.
Massive cerebral infarction with malignant brain edema has poor prognosis with very high mortality, despite aggressive medical treatment. Surgical decompression is recommended by Chinese and international clinical guidelines for patients with massive cerebral infarction, however, there is no standardized diagnosis and treatment protocol in clinical practice. Following the principle of evidence-based medicine and based on the diagnosis and treatment norms of the participating hospitals of Severe Ischaemic Stroke Collaboration in recent years, we recommend this consensus statement of the standardized surgical decompression for malignant brain edema in massive cerebral infarction.