| Part 1 The Association Between APOE Genotypes and Ischemic StrokeOpinions on the association of ischemic stroke (IS) and APOE gene polymorphisms have not been consistent. We explored this relation in a Northwest China Han population. This case-control study involved 513 IS patients and 514 controls without IS from the second hospital of Lanzhou University, whose characteristics and clinical information were collected. MassARRAY iPLEX system was applied to determine the APOE genotypes. After analysis, it is showed that APOE ε4 allele, ε4/ε4 genotype and ε4-containing genotypes were associated with IS (ε4 vs. ε3, p=0.012, OR= 1.491. ε4/ε4 vs. ε3/ε3, p=0.045, OR=8.449. ε4-containing vs. ε3/ε3, p=0.027, OR=1.453). It was showed in the further analysis for IS subtypes according to TOAST classification system that APOE ε2 allele, ε4 allele and ε4/ε4 genotype were associated with large artery atherosclerosis IS subtypes (ε2 vs. ε3, p=0.044, OR=0.500. ε4 vs. ε3, p=0.047, OR=1.614. ε4/ε4 vs. ε3/ε3, p=0.017, OR=16.525). In addition, it was also showed that ε4/ε4 genotype was related to small vessel disease IS (ε4/ε4 vs. ε3/ε3, p=0.028, OR=11.298). The results that ε4 allele was related to undetermined IS was also indicated in this study, as well as the ε3/ε4 genotype and ε4-containing genotypes (ε4 vs. ε3, p=0.028, OR=1.694. ε3/ε4 vs. ε3/ε3, p=0.033, OR=1.806. ε4-containing vs. ε3/ε3, p=0.017, OR=1.868). In the analysis for the nexus between ε4 allele and characteristics, compared to people with non-ε4-containing genotypes, blood level of TC and LDL were higher in cases, controls and all subjects with ε4-containing genotypes. Besides, blood level of TG was higher in controls with ε4-containing genotypes. The proportion of cardiopath history was found higher in all subjects with ε4-containing genotypes. Other clinical information did not relate with APOE ε4-containing genotypes as shown in this study, including age, gender, BMI, HDL, history of hypertension, diabetes, dyslipidemia. In conclusion, in a Northwest China Han population, APOE was a risk gene for ischemic stroke, especially for large artery atherosclerosis IS, and APOE ε4 allele was associated with blood lipid level.Part 2 Different Protein Map Between Ischemic Stroke Patients With APOEε4/ε4 Genotype and ε3/ε3 Genotype.With the development of genomics, the protein products coded by gene gradually came into researcheres’ sight. Two-dimensional electrophoresis technology is one of the main methods to present protein map. We analyzed the different protein spots in plasma between ischemic stroke patients with APOEε4/ε4 genotype and ε3/ε3 genotype.16 patients were recruited into this study, including 8 patients with APOEε4/ε4 genotype and 8 patients with APOEε3/ε3 genotype. Using Aurum Serum Protein Mini Kit to deplete the abundant protein in plasma. Two-dimensional electrophoresis analysis allowed to identification of a specific pattern associated with the ε4/ε4 mutant genotype. Mass spectrometry were taked to confirm the protein spots cutted from gels. After analysis, there are 7 peroteins which were presented different in two genotypes, CLUS, FETUA, AACT, CERU, TRFE, HPT, A2MG, in which, CERU was down-regulation, and others were up-regulation. In summary, APOEε4/ε4 genotype affected the plasma level of acute phase reactive protein, inflammation related proteins, iron metabolism related proteins, lipid metabolism related proteins, and coagulation related proteins. Therefore, APOE gene polymorphism take effect to susceptibility of ischemic stroke not only through lipid metabolism pathway, but also by the other mechanisms. |
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