| Objective:1) To explore the lipid metabolism characteristics of patients with acute ischemic stroke in Xinjiang;2) To investigate the association between the lipid metaboli-sm-related gene polymorphisms, and interactions of genes-genes, gene-environment and risk of IS in Xinjiang;3) To evaluate the effect of lipid metabolism related gene polymer-phisms on the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients in Xinjiang. Methods:1)408patients with ischemic stroke were selected for the present study, confirmed by CT and/or MRI. Their information including ethnicity, age, gender, history of tobacco and alcohol using, blood pressure, fasting blood-glucose, blood lipid and the stability of the atherosclerotic plaques was collected. Patients were divided into LAA/CE/SAO groups, stable plaque/unstable plaque groups, hypertension/non hyperten-sion groups and diabetes/non diabetes groups. The differences of blood lipid level, inclu-deing total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1(ApoAl), apolipoprotein B (ApoB), Lipoprotein (a)[LP (a)] and TC/HDL-C, LDL-C/HDL-C, ApoA1/B ratio, were observed in each group mentioned above;2) A case-control study including408ischemic stroke cases and347unrelated healthy individuals was designed to explore the relationship of lipid related gene polymorphisms and the morbidity of ischemic stroke. Genomic DNA of all selected subjects was extracted. Six lipid related genes,3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), APOA5, lipoprotein lipase (LPL, cholesteryl ester transfer protein CETP, low-density lipoprotein receptor (LDLR), the first protein-converting enzyme9(PCSK9), were selected as candidate genes. And nine SNP loci in the six genes were genotyped by SNaPshot technique and analyzed by GeneMapper4.1. SPSS20.0was used for data management and analysis.Using single locus analysis, the distribution difference of genotypes of loci in ischemic stroke cases and controls were detected to assess the genetic risk factors of ischemic stroke. Ethnicity and gender stratified analysis were carried out to develop further research. Apart from that, combined methods including interaction analysis of multiple genes and loci were employed to explore the association between the lipid metabolism-related gene polymorphisms and IS risk.3) Atorvastatin calcium was used for lipid-lowering treatment, and200ischemic stroke patients finished the3months’therapy. ANOVA analysis of SPSS20.0was conducted to explore the association between gene polymorphisms and effect of atorvastatin calcium on ischemic stroke patients. Results:1) LDL-C、ApoB、TC/HDL-C、LDL-C/HDL-C and ApoAl/B levels were significantly differences in three ischemic stroke subtypes. ApoA1, TC/HDL-C, LDL-C/HDL-C and ApoAl/B levels was significant difference between the LAA group and SAO groups; Compared with CE group, TC, HDL-C, LDL-C, ApoB, TC/HDL-C, LDL-C/HDL-C and ApoAl/B levels were significantly higher than in the LAA group. Compared with CE group, LDL-C, ApoAl, ApoB, TC/HDL-C, LDL-C/HDL-C and ApoAl/B levels were significantly higher in the SAO group.Compared with stable plaque group, unstable plaque group had lower HDL level and significant higher LDL, ApoB, Lp (a), TC/HDL-C, LDL-C/HDL-C and ApoAl/ApoB levels (P<0.05or P<0.01). Hypertension group had significant higher TG, ApoB, Lp (a) levels than non-hypertensive group (T<0.05or P<0.0.1). Diabetic group had significant higher TC, TG, ApoAl, ApoB, TC/HDL-C, LDL-C/HDL-C, ApoAl/ApoB levels than non-diabetic group (P<0.05or P<0.01). Multiple logistic regression analysis revealed that hypertension,diabetes, LDL, ApoB, LDL-C/HDL-C, ApoA1/ApoB might be factors affecting cerebral infarction;2) From analysis of single gene locus, In recessive model, significant differences (P<0.05) of genotype distrution in ischemic stroke cases and controls were observed in rs688, and differences were observed in BMI levels of rs2266788(P<0.05), TG levels of rs328(P<0.05) and systolic blood pressure of rs708272(P<0.05) among different genotypes in total studied population. In recessive model, significant differences (P<0.05) of genotype distrution in ischemic stroke cases and controls were observed in rsl2916, rs3846662and rs688in Han population.There are not significant difference between genotype distrution in ischemic stroke cases and controls. In binary logistic regression analysis of total studied population, ischemic stroke was observed significantly associated with rs688both in addictive model (TT/CC, adjusted OR=1.47,95%CI=1.04-2.07, P<0.01)and recessive model (TT/CT+CC, adjusted OR=2.66,95%CI=1.37-5.14,P<0.01). In Han population, ischemic stroke was observed significantly associated with rs688both in addicitive model (TT/CC, adjusted OR=3.27,95%CI=1.06-10.05, P<0.05) and recessive model (TT/CT+CC, adjusted OR=331,95%CI=1.08-10.10, P<0.05), and rs3846662in recessive model (AA/GA+GG, adjusted OR=1.60,95%CI=1.00-2.57, P<0.05). In Uighur population, no significant association was found between gene polymorphisms and the risk of ischemic stroke. Combined analysis of multiple genes and loci, interaction effects of LDLRrs688C/T, HMGCRrs3846662C/T, ApoA5rs662799A/G and CETPrs708272C/T denoted a significant influence on IS susceptibility (P<0.05). Multiple logistic regression analysis revealed that total locis were interaction with hypertension in IS.3) Significant differences were found in ALDL (after treatment-pre-treatment) and ΔLDL/LDL (before treatment) of rs662799(P<0.05), ΔLDL/LDL (before treatment) and Δ (LDL/HDL)/(LDL/HDL) of rs320(P<0.01), ΔLDL (after treatment-pre-treatment) of rs708272(P<0.05) among different genotypes in total studied population. In Han population, significant differences were observed in ΔTG (after treatment-pre-treatment) of rs662799(P<0.05), ΔLDL/LDL (before treatment) and Δ (LDL/HDL)/(LDL/HDL) of rs320(P<0.01) among different genotypes. In Uighur population, significant differences were observed in AHDL (after treatment-pre-treatment) of rs2266788(P<0.05), ALDL/LDL (before treatment) of rs662799(P<0.05) and ALDL (after treatment-pre-treatment) of rs708272(P<0.05) among different genotypes.Conclusion:1) Blood lipid levels of patients with ischemic stroke were significantly associated with the different stroke subtypes, plaque stability, hypertension and hyperglycemia;2) From analysis of single gene locus, rs688polymorphisms of LDLR gene were significantly associated with the morbidity of ischemic stroke in Chinese, especially Han people; From analysis of multiple gene locus, interaction effects of LDLRrs688C/T, HMGCRrs3846662C/T, ApoA5rs662799A/G and CETPrs708272C/T maybe influence on IS, and these nine locis were interaction with hypertension in IS.3) Polymorphisms of rs662799and rs2266788in APOA5gene, rs320in LPL gene and rs708272in CETP gene had significant association with the effect of the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients. |
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