Relationship between R219K polymorphism of adenosine triphosphate-binding cassette transporter 1 gene and cerebral infarction: A case-controlled analysis

BACKGROUND： Studies have shown that adenosine triphosphate-binding cassette transporter 1 （ABCA1） gene influences atherosclerosis. Studies have also demonstrated that cerebral infarction does not occur often in pre-menopausal women. It has been, therefore, assumed that sex plays a role in R219K polymorphism of ABCA1 gene and cerebral infarction. OBJECTIVE： To explore the relationship between lipid metabolism-correlated R219K polymorphism of ABCA1 gene, risk factors of cerebral infarction and lipid level, and to determine whether there were significant differences in gender between R219K polymorphism of ABCA1 gene and cerebral infarction. DESIGN, TIME AND SETTING： A multicentral and non-randomized, controlled study based on gene polymorphism was performed at the Chinese National Human Genome Center, and lipid concentrations were measured at Beijing Xuanwu Hospital. Patients with cerebral infarction and healthy subjects were enrolled from eight hospitals of six provinces of China between October 2002 and December 2004. PARTICIPANTS： There were 177 patients in the cerebral infarction group, including 119 males and 58 females, with a mean age of （60 -＋ 13） years, and 234 healthy subjects in the normal control group, including 79 males and 155 females, with a mean age of （58 ± 12） years. METHODS： R219K polymorphism of the ABCA1 gene was detected using polymerase chain reaction-restriction fragment length polymorphism, and blood lipid concentrations were simultaneously measured. MAIN OUTCOME MEASURES： Genotype and allele frequency of R219K polymorphic site, and blood lipid concentrations. RESULTS： RR genotype and R allele frequency of males in the cerebral infarction were significantly greater than males in the normal control group [RR genotype： x2 = 5.305, OR （95% CO, 2.326 （1.120 4.828）, P〈 0.05; R allele： x2= 4.219, OR （95% CO, 1.528 （1.019 2.292）, P〈 0.05]. In addition, RR genotype and R allele frequency of males were significantly greater than females in the cerebral infarction group [RR genotype： x2= 5.172, OR （95% C/）, 2.604 （1.120-6.057）, P〈 0.05; R allele： x2= 4.818, OR （95% CO, 1.652 （1.053 2.589）, P〈 0.05]. There were no significant differences between genotype and lipid concentrations between the two groups （P〉 0.05）. CONCLUSION： The RR genotype of ABCA1 R219K might be associated with onset of cerebral infarction in males, but blood lipid concentrations do not relate to R219K polymorphism.

Relationship between the -455G/A and -148C/T polymorphisms in the beta-fibrinogen gene and cerebral infarction in the Xinjiang Uygur and Han Chinese populations

We sought to investigate the correlation between the -455G/A and -148C/T polymorphisms of the β-fibrinogen gene and plasma fibrinogen levels in patients with cerebral infarction and in healthy subjects among the Xinjiang Uygur and Han Chinese populations, by using polymerase chain reaction-restriction enzyme digestion analysis. Results showed that there were no statistically significant differences in the distributions of the -455G/A genotype and allele frequency between the Uygurs and the Han. Plasma fibrinogen levels in cerebral infarction patients among the Uygurs and the Han were higher than those among healthy subjects. In particular, the frequencies of the -455G/A AA and -148C/T TT genotypes were significantly higher than in healthy subjects. Individuals carrying the A or T allele had a higher incidence of cerebral infarction compared with those carrying the G or C allele. Our experimental findings indicate that the -148C/T and -455G/A polymorphisms are associated with cerebral infarction in Xinjiang Uygur and Han Chinese subjects. The susceptibility- conferring alleles are -148T and -455A, and the susceptibility-conferring genotype is -455G/A ＋ AA.

A Meta-analysis of β-fibrinogen Gene-455G/A Polymorphism and Plasma Fibrinogen Level in Chinese Cerebral Infarction Patients

Objective To evaluate the correlation between the β-fibrinogen gene-455G/A polymorphism and cerebral infarction in Chinese population by means of meta-analysis. Methods Genetic association studies on evaluating the β-fibrinogen gene -455G/A polymorphism and cerebral infarction involving Chinese population published before December 2005 were collected from database of PubMed, EMBASE, and CNKI. All the data in literature were abstracted based on the defined selection criteria by two independent investigators. Publication bias was tested by funnel plot and the odd ratios of all studies were combined dependent on the result of heterogeneity test among the individual studies. The software Review Manager （Version 4.2） was used for meta-analysis. Results Eleven studies including 1405 patients and 1600 controls met the selection criteria. There was no publication bias in 11 reviewed studies. Heterogeneity test of reviewed studies showed statistically significant differences （χ^2=24.58, P=0.006） among the ORs of individual studies. The combined OR of 11 studies of susceptibility to cerebral infarction in –455A allele carriers compared with the -455G/G wild homozygotes was 1.33 （95%CI 1.04-1.71, P=0.02）. In the patients with cerebral infarction in 6 studies, the summarized average plasma fibrinogen level of allele A carrier was 0.29 g/L （95%CI 0.14-0.44, P=0.0002） higher than that of -455G/G homozygous ones. Conclusions β-fibrinogen gene -455G/A polymorphism might contribute to susceptibility of cerebral infarction in Chinese population; allele A increases the individual susceptibility to the disease.

Plasma fibrinogen beta-148C/T gene polymorphism in cerebral infarction patients

BACKGROUND： Plasma fibrinogen （Fg） β-148C/T gene polymorphism is a risk factor for ischemic angiopathy. OBJECTIVE： To explore the frequency distribution of Fg β- 148C/T gene polymorphism and its relationship with plasma Fg levels in patients with cerebral infarction. DESIGN, TIME AND SETTING： Case control experiment of gene polymorphism was performed at the Central Laboratory of Qingdao University Medical College from January 2003 to June 2004. PARTICIPANTS： A total of 88 patients with cerebral infarction were recruited from the Affiliated Hospital of Qingdao University Medical College, including 52 males and 36 females, averaging （61±14） years of age In addition, 80 healthy cases served as the control group, comprising 48 males and 32 females, with an average age of （58 ± 12） years. METHODS： Blood DNA was extracted, and electrophoresis results were observed using an ultraviolet single photon image system. The frequency distribution of Fg β -148C/T was analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Plasma Fg levels were measured by cerebral infarction time. MAIN OUTCOME MEASURES： Plasma Fg β -148C/T gene polymorphism and plasma Fg levels in patients with cerebral infarction. RESULTS： The frequency of the T allele, and plasma Fg levels in CC, CT, and CC＋CT genotype subgroup, were significantly greater in the cerebral infraction group, compared with the control group （P 〈 0.05）. However, there was no significant difference between the TT genotype subgroup and the control group （P 〉 0.05）. The plasma Fg levels in the CT, TT, and CT＋TT genotype groups were significantly greater than the CC genotype group （P 〈 0.05）. However, in the control group, plasma Fg levels in the TT genotype subgroup were significantly greater than the remaining genotype subgroups （P 〈 0.05）. CONCLUSION： Plasma Fg β -148C/T gene polymorphism is an important hereditary factor for differences in plasma Fg levels. The T allele plays a crucial role in influencing plasma Fg levels in cerebral infarction. Fg β - 148C/T may be a susceptibility factor for cerebral infarction.

Analysis of relationship between cerebral infarction and behavioral factors and gene polymorphism of Bβ-FBG-455G/A by Logistic analysis

Objective To investigate the relationship between FBG levle,and pol;ymorphism of Bβ FBG 455G/A and other associated factors in patients with cerebral infarction.Method The relationship between FBG level,polymorphism of Bβ FBG 455G/A and related factors such as risk factors,hypertension,diabetes,smoking were analyzed by using logistic regression.Result The principal risk factors related to cerebral infarction are hypertension,smoking,diabetes,FBG,and polymorphism of Bβ FBG 455G/A related to FBG.Conclusion FBG is another risk factor of stroke besides hypertension,smoke,and diabetes.

Correlation between peripheral blood Cx40 gene polymorphism and atherosclerotic plaque property development in patients with cerebral infarction

Objective:To study the correlation between peripheral blood connexin 40 (Cx40) gene polymorphism and atherosclerotic plaque property development in patients with cerebral infarction.Methods: Patients who were treated in the Second Affiliated Hospital of Xi'an Medical University due to acute cerebral infarction between March 2015 and March 2018 were selected as cerebral infarction group, and healthy subjects who received physical examination during the same period were selected as control group. Peripheral blood was collected to detect the polymorphism of Cx40 gene rs35594137 locus, and serum was collected to determine the contents of cytokines, proteases and related molecules.Results: The constituent ratio of Cx40 gene AA+AG genotype in peripheral blood of cerebral infarction group was higher than that of control group whereas the constituent ratio of GG genotype was lower than that of control group;serum IL-17, HMGB1, VCAM1, MCP-1, P-selectin, YKL-40, MMP9, TIMP1 and Caspase-3 contents as well as MMP9/TIMP1 ratio of cerebral infarction group were significantly higher than those of control group whereas ADAMTS13 and Vaspin contents were significantly lower than those of control group;serum IL-17, HMGB1, VCAM1, MCP-1, P-selectin, YKL-40, MMP9, TIMP1 and Caspase-3 contents as well as MMP9/TIMP1 ratio of cerebral infarction group of patients with CX40 gene AA+AG genotype were significantly higher than those of patients with GG genotype whereas ADAMTS13 and Vaspin contents were significantly lower than those of patients with GG genotype.Conclusion: The mutation from Cx40 gene rs35594137 allele G to A in peripheral blood of patients with cerebral infarction can promote the development of atherosclerotic plaque properties.

Effect of paraoxonase1 gene polymorphism on carotid plaque and cerebral infarction in Hainan population

Objective:To investigate the effect of paraoxonase 1 gene polymorphism on carotid plaque stability with cerebral infarction in Hainan population.Methods:277 patients of caroticl plaque With cerebral infarction who underwent physical examination in a hospital in Hainan from 2015 to another awarding 2018 were selected as the experimental group and the 363 people who no cerebral infarction as the Analytical methods:control group.The clinical data analyzed.DNA was collected from peripheral blood of two groups of patients and genotyped by flight mass analytical methods.''AG and GG could be detected by rs3917538.The distribution frequencies of The three genotypes in The control group accorded with Hardy-Weinberg equilibrium.Results:The distribution frequencies of AA,AG and GG in the control group were 97(26.7%),175(48.2%)and 91(25.1%)respectively.In the experimental group,the distribution frequencies were 76(27.4%),136(49.1%)and 65(23.5%).There were no statistical differences among the three detection methods of co-dominant model,Dominant model and recessive model.There was no difference in the frequency of allele A and G between groups.Conclusion:Polymorphism of paraoxonase 1 gene rs3917538 has No significant effect on carotid plaque formation and cerebral infarction in Hainan population.The Supplementary sample size to add more SNP research sites for further study,It is expected to further Revral the relationship between PON1and carotial piaque complicatecl with cerebral infarction in Hainan.

Association of IL33/ST2 Signal Pathway Gene Polymorphisms with Myocardial Infarction in a Chinese Han Population

This study investigated the relationship between IL-33/ST2 signal pathway gene polymorphisms and myocardial infarction（MI） in Han Chinese. A case-control association analysis was performed on a total of 490 MI patients（MI group） and 929 normal subjects（NC group）. Sequenom Mass Array and Taqman genotyping technique were used to analyze the tag single nucleotide polymorphisms（SNPs） in the genes encoding IL-33, ST2, and IL-1Ra P（rs11792633, rs1041973 and rs4624606）. The results showed that the frequencies of rs4624606 genotypes AA, TT, AT were 0.031, 0.647, 0.322 in MI group and 0.026, 0.712, 0.263 in NC group, and the allele frequencies of A and T were 0.192, 0.808 in MI group and 0.157, 0.843 in NC group. There were significant differences in rs4624606 genotypes and allele frequencies between MI group and NC group（P〈0.05）. For rs11792633, the allele frequencies of C and T were 0.45, 0.55 in MI group and 0.454, 0.546 in NC group with no significant differences found between the two groups. Compared with genotype CC＋TC, rs11792633 genotype TT had an increased risk of hypertension（P〈0.05）. However, there were no significant differences in the frequencies of rs11792633 genotypes between the two groups. No significant differences were noted in the frequencies of rs1041973 genotype and allele between the two groups. Logistic regression analysis showed that rs4624606 genotypes AT and AA＋AT were both significantly associated with MI（AT： OR=1.325, P=0.029, 95% CI=1.03–1.705; AA＋AT： OR=1.316, P=0.028, 95% CI=1.03–1.681） after factors such as age, gender, smoking, drinking, body mass index（BMI）, triglyceride（TG） and cholesterol were adjusted. Those carrying rs4624606 genotype AT or AA＋AT had an increased risk of MI. No associations were found between the polymorphisms of the other two loci with MI. It was concluded that, in the IL33/ST2 signal pathway, the A allele of rs4624606 polymorphism of IL-1Ra P gene is a potential independent risk factor for MI, and the genotypes AA＋AT and AT are associated with the incidence of MI.

Correlation between angiotensinogen gene and primary hypertension with cerebral infarction in the Li nationality of China

Objective To investigate the relationship of four single nucleotide polymorphism （SNP） haplotypes in the angiotensinogen （AGT） gene to the primary hypertension with or without cerebral infarction in the Li nationality of Hainan, China. Methods Total 300 subjects were allocated into three different groups： Groupl, 100 patients who have primary hypertension; Group 2, 100 patients who have primary hypertension with cerebral infarction; and control group, 100 healthy individuals. The genotypes of all subjects were determined by PCR-sequencing to analyze the four poly- morphisms at position - 152 （G-A）, -20 （A-C）, - 18 （C-T）, and -6 （A-G） in the promoter region of AGT. Results The frequen- cies ofCT genotype of AGT-18 and T allele in Group 1 （P = 0.003, P = 0.004） and Group 2 （P = 0.002, P = 0.002） were both significantly higher than in healthy controls. The frequency of G allele of AGT-6 was significantly higher in Group 2 than in the control group （P = 0.016）, while there is no significant difference between Group 1 and the control. Haplotype analysis revealed that H6 haplotype frequency which included -20C and -6G was significantly increased in Group 2 （P = 0.003） compared with the control group, while H5 haplotype frequency which included -20C and -18T was signifi- cantly increased in Group 1 （P = 0.006） versus the control. Conclusion The -20 （A-C） and - 18 （C-T） of the AGT may play an important role in pathogenesis of primary hypertension; and -20 （A-C）, -18 （C-T）, and -6 （A-G） may be the genetic risk factors for the onset of primary hypertension with cerebral infarction in the Li nationality of Halnan, China.

Tag single nucleotide polymorphism rs1532624 located in cholesteryl ester transfer protein gene is associated with atherosclerosis cerebral ischemia

Objective: To investigate the relationship between polymorphisms of rs1532624 and rs289741 loci in cholesteryl ester transfer protein(CETP) genes and atherosclerotic cerebral infarction(ACI). Methods: The CETP gene rs1532624 and rs289741 in 95 patients with ACI and 177 healthy subjects were genotyped by Mass ARRAY mass spectrometry. Each locus genotype and allele frequency distributions were compared. Results: The difference of allele frequency distribution between the rs1532624(χ~2=1.723, P=0.189) and rs289741(χ~2=2.466, P=0.116) were not statistically significant. The frequency distribution of rs1532624 genotype between the cerebral infarction group and healthy control group was statistically significant(χ~2=7.096, P=0.029), while rs289741 genotype frequency distribution between the two groups was not statistically significant(χ~2=2.906, P=0.234). Conclusion: ACI have a positive correlation with rs1532624 polymorphism, and AA genotype may be susceptible factors of ACI.

Association of plasminogen activator inhibitor-1 4G/5G promoter polymorphism with recurrent cerebral infarction in China’s North Jiangsu Province

BACKGROUND： Many international studies have shown that plasminogen activator inhibitor-1 （PAl-l） 4G/5G promoter polymorphism does not increase the risk for cerebral infarction. OBJECTIVE： Using PCR methodology and agarose electrophoresis to detect PAI-1 4G/5G promoter polymorphism in patients with recurrent cerebral infarction in the North Jiangsu Province of China, and to compare results with healthy subjects and patients with first-occurrence cerebral infarction in the same region. DESIGN, TIME AND SETTING： Non-randomized, concurrent, control trial. A total of 122 cerebral infarction patients were admitted to Xuzhou Medical College Hospital＇s Department of Neurology and Xuzhou Central Hospital＇s Department of Neurology between July 2003 and August 2006. PARTICIPANTS： The patients consisted of 63 males and 59 females, aged （62 ± 10） years. They were divided into first-occurrence （n = 58） and recurrence （n = 64） groups. In addition, 50 healthy subjects that underwent physical examination in the outpatient department, including 26 males and 24 females, aged （60 ±12） years, were selected as controls. METHODS AND MAIN OUTCOME MEASURES： PAl-1 4G/5G promoter polymorphism was detected and analyzed using PCR methodology and agarose electrophoresis. RESULTS： Significant differences were determined in terms of genotypic frequency and allele frequency of PAI-1 4G/5G promoter polymorphism, in patients with first-occurrence or recurrent cerebral infarction, when compared with healthy subjects （P 〈 0.05）. There was, however, no significant difference between the first-occurrence and recurrence groups （P 〉 0.05）. CONCLUSION： PAl- 1 4G/5G promoter polymorphism is genetic risk factor for cerebral infarction in China. However, it may be associated with recurrence of cerebral infarction in patients from the North Jiangsu Province of China.

Apolipoprotein E gene polymorphism in cerebrovascular diseases of the Chinese Naxi populations from Yunnan province

Currently it is not well known whether apolipoprotein E （ApoE） is a genetic susceptibility factor for cerebrovascular diseases in the Chinese Naxi population. The present study detected and sequenced ApoE polymorphisms of 90 patients with cerebrovascular diseases （58 cases of cerebral infarction and 32 cases of intracerebral hemorrhage）, and 50 normal people of Naxi nationality from Yunnan province, China. The populations were used to analyze the relationship of ApoE polymorphisms with cerebral infarction and intracerebral hemorrhage. Results showed an association between ApoE gene polymorphism and the onset of cerebral infarction, and a possibility that the ε4 allele is a susceptibility locus for the risk of cerebral infarction. However, there was no evidence of a relationship between the ApoE gene polymorphism and cerebral hemorrhage.

APOLIPOPROTEIN(a) AND CORTICAL CEREBRAL INFARCTION

Objective. The present study aimed to elucidating the correlation of apolipoprotein(a)[apo(a)] with cerebral infarction at the levels of molecule and protein. Methods. The serum Lp(a) level, by means of ELISA, the polymorphism of apo(a) protein, by SDS PAGE/Western blotting combined with silver staining assays, and the sequence polymorphisms in 5’ control region, the first exon and intron of apo(a)gene, by PCR SSCP/AFLP assays, were detected in 85 healthy controls and 42 cases of cortical cerebral infarction. Results. The serum Lp(a) level was markedly higher in the patients(152.59±3.41 mg/L)than that in the controls(56.21±3.67 mg/L)(t=4.15, P<0.001), even between the subjects with the same apo(a) phenotype. The frequency of low molecular weight phenotype was significantly higher in the patients than that in the controls(0.5238 vs. 0.2941). There were 2 sites of sequence variance in the 5’ control region of apo(a) gene in our studied population, which were of significant difference between patients and controls, and were related to the variation of serum Lp(a) level. Conclusion. Our study found that the low molecular weight phenotype of apo(a) was closely associated with cerebral infarction, suggested that the variation of serum Lp(a) level be determined by not only the size of apo(a) gene but also its sequence, which indicated that both the size and sequence of apo(a) are associated with the susceptibility to cerebral infarction.

A meta-analysis of relationship between β-fibrinogen gene-148C/T polymorphism and susceptibility to cerebral infarction in Han Chinese

Objective The results of studies on association between -148C/T polymorphism in promoter region of β3-fibrinogen gene and susceptibility to cerebral infarction in Chinese population are controversial. In this study, we summarize the results of published works in this field by a meta-analysis. Data sources Genetic association studies evaluating the β-fibdnogen gene -148C/T polymorphisms and cerebral infarction involving Chinese population published before December 2005 were collected from PubMed, EMBASE and CNKI. Study selection Case control studies involving unrelated, Han subjects aged from 18 to 80 years, and the internationally recognized diagnostic standard of cerebral infarction and genotype frequencies in control group consistent with Hardy-Weinberg equilibrium were used. Publication bias was tested by funnel plot and the odds ratios of all studies were combined dependent on the result of heterogeneity test among the individual studies. The software Review Manager （Version 4.2） was used for meta-analysis. Results Eleven studies including 1223 patients and 1433 controls met the selection criteria. There was no heterogeneity among the odds ratios （ORs） of individual studies （Х^2=17.82, P=0.06）. The combined OFt of susceptibility to cerebral infarction in -148T allele carriers compared to the wild homozygote was 1.32 （95%CI 1.12 to 1.55, P=-0.0008）. In the patients with cerebral infarction, the average plasma fibrinogen level of allele T carrier was 0.42 g/L （95% CI 0.29 to 0.54, P〈0.001）, higher than that of -148C/C homozygous ones. Conclusions β3-fibrinogen gene -148C/T polymorphism might contribute to susceptibility to cerebral infarction in Han Chinese. To reach a definitive conclusion, further gene to gene and gene to environment interactions studies on β3-fibrinogen polymorphisms and cerebral infarction with large sample size are required.

CYP2C19基因多态性联合生化指标预测脑梗死患者氯吡格雷抵抗的价值分析

目的探究CYP2C19基因多态性和生化指标联合预测脑梗死患者氯吡格雷抵抗(CR)的价值。方法选取首都医科大学附属北京天坛医院2021年1月至2023年12月收治的387例脑梗死患者作为研究对象,根据患者入院后血小板聚集试验-二磷酸腺苷(PAgT-ADP)的检测结果将脑梗死患者分为氯吡格雷有效组(PAgT-ADP≤43%)和CR组(PAgT-ADP>43%)。观察脑梗死患者CYP2C19基因分型的分布情况,并回顾性分析两组患者的年龄、性别和生化指标[包括尿素、肌酐(Cr)、尿酸(UA)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)、乳酸脱氢酶(LDH)、三酰甘油(TG)、总胆固醇(CHO)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)、同型半胱氨酸(Hcy)]。对统计指标进行单因素分析,通过多因素Logistic回归分析构建联合预测模型,绘制受试者工作特征(ROC)曲线分析CYP2C19基因代谢类型单独及联合生化指标对预测脑梗死患者CR的效能。结果CR组和氯吡格雷有效组性别、Cr、TBIL、DBIL、IBIL、Hcy及CYP2C19基因代谢类型比较差异均有统计学意义(P<0.05);多因素Logistic回归分析结果显示,Cr、ALT、AST、TBIL、DBIL、IBIL、CHO、LDL、CYP2C19基因代谢类型为脑梗死患者CR的独立预测因子(P<0.05);ROC曲线分析结果显示,联合预测模型预测脑梗死患者CR的曲线下面积为0.720,灵敏度和特异度分别为71.1%和65.5%,而CYP2C19基因代谢类型单独预测脑梗死患者CR的曲线下面积为0.641,灵敏度和特异度分别为67.3%和56.9%,联合预测模型的曲线下面积与CYP2C19基因代谢类型的曲线下面积比较差异有统计学意义(P<0.05)。结论CYP2C19基因多态性联合生化指标有助于预测脑梗死患者CR的发生,尤其对于CR而CYP2C19基因代谢型表现为正常代谢的患者有较好的预测价值。

黑龙江地区老年脑梗死患者CYP2C19基因多态性对氯吡格雷疗效的影响

目的探讨黑龙江地区脑梗死患者接受氯吡格雷治疗时CYP2C19基因多态性对治疗效果的影响。方法选取2022年1—12月在黑龙江省医院神经内科住院的90例脑梗死患者为研究对象。检测CYP2C19基因多态性,根据检测结果,将患者分为3组,快代谢组(n=26)、中等代谢组(n=52)和慢代谢组(n=12)。所有患者均给予氯吡格雷治疗,对美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分及预后情况进行观察对比。结果在脑梗死患者中以快代谢型和中等代谢型为主要类型。治疗2周后,3组NIHSS评分低于治疗前,差异有统计学意义(P<0.05);且快代谢组评分为(6.23±1.38)分,低于中等代谢组、慢代谢组的(7.76±1.71)分、(10.12±1.29)分,差异有统计学意义(P<0.05);快代谢组和中等代谢组预后良好率高于慢代谢组(P<0.05);快代谢组、中等代谢组和慢代谢组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论通过对老年脑梗死患者行CYP2C19基因型检测来评估对氯吡格雷治疗的药物代谢能力和反应情况。有助于制定个体化的治疗方案,提高治疗效果并降低不良反应的发生率,可以最大限度地提高治疗效果,减少风险发生。

血清SIRT1、Fibulin-5、Bcl-2/Bax与颈动脉粥样硬化斑块破裂所致脑梗死的关系及联合检测价值

目的 探讨血清沉默信息调节蛋白1 (SIRT1)、衰老关键蛋白抗原-5 (Fibulin-5)、B淋巴细胞瘤基因-2(Bcl-2)/B淋巴细胞瘤基因-2相关X蛋白(Bax)与颈动脉粥样硬化(CAS)斑块破裂所致脑梗死(ACI)的关系及联合检测价值。方法 选取新疆维吾尔自治区人民医院2021年1月至2023年2月CAS斑块破裂所致ACI患者98例作为研究组,另选取同期CAS斑块未破裂患者98例作为对照组,比较两组血清SIRT1、Fibulin-5、Bcl-2、Bax水平,分析各血清指标对CAS斑块破裂所致ACI风险的影响及与病情的关系,并评价各血清学指标单独及联合预测CAS斑块破裂所致ACI的价值。结果 研究组血清SIRT1、Bcl-2水平低于对照组,Fibulin-5、Bax水平高于对照组(P<0.05);大面积梗死(MCI)患者血清SIRT1、Bcl-2水平<小面积梗死患者<腔隙性梗死(LI)患者,Fibulin-5、Bax水平>小面积梗死患者> LI患者(P<0.05);重度神经功能缺损患者血清SIRT1、Bcl-2水平<中度神经功能缺损患者<轻度神经功能缺损患者,Fibulin-5、Bax水平>中度神经功能缺损患者>轻度神经功能缺损患者(P<0.05);血清SIRT1、Bcl-2低水平患者CAS斑块破裂所致ACI风险是高水平患者的2.311倍、2.921倍,Fibulin-5、Bax高水平患者CAS斑块破裂所致ACI风险是低水平患者的3.470倍、3.184倍(P<0.05);血清SIRT1、Bcl-2与梗死面积、神经功能缺损程度呈负相关,Fibulin-5、Bax与梗死面积、神经功能缺损程度呈正相关(P<0.05);血清SIRT1、Fibulin-5、Bcl-2、Bax预测CAS斑块破裂所致ACI的AUC分别为0.716 (95%CI:0.648~0.778)、0.796 (95%CI:0.733~0.850)、0.728 (95%CI:0.660~0.789)、0.763 (95%CI:0.698~0.821),联合预测CAS斑块破裂所致ACI的AUC为0.909 (95%CI:0.860~0.945),优于各血清指标单独预测。结论 血清SIRT1、Fibulin-5、Bcl-2/Bax与CAS斑块破裂所致ACI及其病情程度密切相关,联合预测价值可靠,对临床开展防治工作具有指导意义。

CYP2C19基因多态性、血清NT-proBNP水平与急性脑梗死静脉溶栓预后不良的关系

目的探讨CYP2C19基因多态性、血清N末端B型脑利钠肽前体(NT-proBNP)水平与急性脑梗死(ACI)患者静脉溶栓预后不良的关系。方法选择210例ACI患者,均行阿替普酶静脉溶栓治疗,治疗90 d后根据改良Rankin量表(mRS)评分将患者分为预后不良组(mRS评分≥3分)52例、预后良好组(mRS评分<3分)158例。治疗前采用实时荧光定量PCR法检测CYP2C19基因多态性,时间分辨荧光免疫层析法检测血清NT-proBNP。用Pearson或Spearman分析CYP2C19基因多态性、血清NT-proBNP水平与mRS评分的相关性;用多因素Logistic回归分析ACI患者静脉溶栓预后的影响因素;用受试者工作特征曲线分析CYP2C19基因多态性、血清NT-proBNP水平对ACI患者静脉溶栓预后不良的预测价值。结果预后不良组年龄、高血压比例、糖尿病比例、入院美国国立卫生研究所脑卒中(NIHSS)评分、空腹血糖水平高于预后良好组(P均<0.05)。预后不良组和预后良好组CYP2C19基因多态性比较差异有统计学意义(P<0.05),预后不良组血清NT-proBNP水平高于预后良好组(P<0.05)。ACI患者CYP2C19基因多态性(r_(s)=0.362)、血清NT-proBNP水平(r=0.426)与mRS评分均呈正相关(P均<0.05)。高NIHSS评分、CYP2C19基因慢代谢型、高血清NT-proBNP水平是ACI患者预后不良的危险因素(P均<0.05)。CYP2C19基因多态性、血清NT-proBNP水平单独及联合预测ACI患者静脉溶栓预后的曲线下面积分别为0.752、0.786、0.861,二者联合预测的曲线下面积高于单独预测(P均<0.05)。结论CYP2C19基因多态性和高水平NT-proBNP是ACI患者静脉溶栓预后不良的危险因素,二者联合对不良预后有较高的预测价值。

PON1 Q192R基因多态性与氯吡格雷治疗的脑梗死患者复发相关性研究

目的研究PON1基因多态性及其与氯吡格雷治疗脑梗死患者复发的相关性。方法选取2012年10月—2019年3月河北中石油中心医院接受氯吡格雷治疗的脑梗死患者共205例,根据纳入排除标准,最终纳入169例患者为研究对象。应用原位杂交技术检测PON1 Q192R和CYP2C19基因。将未发生基因突变的患者纳入QQ组(61例),发生基因突变的患者纳入QR+RR组(108例)。计算相对危险度,分析PON1 Q192R基因与脑梗死患者复发的相关性。结果两组患者90 d和1年内脑梗死复发率比较,差异无统计学意义(P>0.05);同一CYP2C19基因型背景下,两组患者90 d和1年内脑梗死复发率比较,差异无统计学意义(P>0.05)。90 d和1年内,QR+RR组患者脑梗死复发的相对危险度分别为1.2、1.3,PON1 Q192R基因与脑梗死复发率呈弱相关。结论PON1 Q192R基因多态性可能是脑梗死患者90 d和1年内复发的遗传易感因素。

CYP2C19基因多态性、miR-374b-5p与ACI患者神经功能缺损和近期预后的关系

目的探讨细胞色素P4502C19(CYP2C19)基因多态性、血清miR-374b-5p水平与急性脑梗死(ACI)患者神经功能缺损和近期预后的关系。方法选取2019年1月—2022年12月郑州市第七人民医院ACI患者164例,收集所有患者的一般资料,并检测CYP2C19基因型和血清miR-374b-5p相对表达量。采用美国国立卫生研究院卒中量表(NIHSS)评估ACI患者神经功能缺损程度。根据治疗15 d后的NIHSS评分将ACI患者分为预后良好组和预后不良组。采用Spearman相关分析评估miR-374b-5p与入院时NIHSS评分的相关性。采用多因素Logistic回归分析评估ACI患者近期预后不良的危险因素。采用受试者工作特征(ROC)曲线评估CYP2C19基因型和血清miR-374b-5p判断ACI患者近期预后的效能。结果164例ACI患者CYP2C19基因型中,GG型(野生纯合子)26例(15.86%)、GA型(突变杂合子)66例(40.24%)、AA型(突变纯合子)72例(43.90%)。A等位基因频率为64.02%,G等位基因频率为35.98%。基因型分布符合Hardy-Weinberg平衡定律(χ^(2)=2.620,P=0.106)。GG基因型、GA基因型、AA基因型的ACI患者入院时NIHSS评分依次升高(P<0.001)。血清miR-374b-5p相对表达量与入院时NIHSS评分呈负相关(r_(s)=-0.510,P<0.001)。ACI患者预后不良发生率为19.51%(32/164)。预后不良组与预后良好组之间年龄、梗死体积、发病至就诊时间、白细胞(WBC)计数、CYP2C19基因型为AA型所占比例和血清miR-374b-5p相对表达量差异均有统计学意义(P<0.05)。梗死体积、发病至就诊时间、WBC计数、CYP2C19基因型为AA型均是ACI患者预后不良的危险因素(P<0.05),miR-374b-5p相对表达量为保护因素(P=0.007)。AA基因型和血清miR-374b-5p单项检测和联合检测判断ACI患者预后不良的曲线下面积(AUC)分别为0.631、0.730、0.802。结论CYP2C19基因多态性、血清mi R-374b-5p相对表达量均与ACI患者神经功能缺损有关,或可作为ACI患者近期预后的评估指标。