NOTCH3基因外显子区rs3815188单核苷酸多态性与徐州地区汉族人群缺血性脑卒中及其亚型的相关性

目的探讨NOTCH3基因外显子区rs3815188单核苷酸多态性与中国徐州地区汉族人群缺血性脑卒中的关系。分析NOTCH3基因rs3815188位点基因多态性对缺血性脑卒中(TOAST分型)发病的影响。方法采用病例-对照研究方法,入选缺血性脑卒中445例(脑卒中组)和同期门诊体检者200例(对照组)。应用PCR-RFLP方法进行NOTCH3基因分型。比较各基因型和等位基因频率分布与缺血性脑卒中及其亚型的关系。结果脑卒中组按TOAST分型,其中大动脉粥样硬化性脑卒中(LAA)214例、小动脉闭塞性脑卒中(SAO)203例。脑卒中组AA及AG基因型频率均低于对照组(χ2=8.158,P=0.017),A等位基因频率显著低于对照组(χ2=4.897,P=0.027,O R=0.7 6 5,95%CI:0.604~0.970)。LAA亚组与对照组比较,AA、AG及GG基因型差异无统计学意义;SAO亚组A等位基因频率显著低于对照组(χ2=5.986,P=0.014,OR=0.707,95%CI:0.535~0.934)。多变量Logistic回归分析显示A等位基因是缺血性脑卒中及SAO亚型的独立保护性因素(P=0.011,OR=0.634,95%CI:0.457~0.905;P=0.007,OR=0.564,95%CI:0.372~0.854);高血压病、糖尿病、冠心病等是缺血性脑卒中发生的独立危险因素。结论中国徐州地区汉族人群中,NOTCH3基因外显子区rs3815188位点单核苷酸多态性可能与缺血性脑卒中发生风险相关;携带A等位基因可能是缺血性脑卒中的独立保护因素,尤其在SAO。     

梅州地区TLR4基因多态性与缺血性脑卒中发病风险的关联研究

目的检测梅州地区缺血性脑卒中患者和健康对照人群Toll样受体4(TLR4)基因的4个多态性位点rs10759932、rs11536879、rs11536891、rs1927914的基因型,分析其与缺血性脑卒中的相关性。方法收集2018年1月1日—2018年7月31日在中山大学附属梅州医院住院治疗的突发缺血性脑卒中患者186例作为病例组,同期在体检中心收集体检健康者194名作为对照组,所有观察对象均为梅州籍。应用Massarray SNP分型技术检测两组患者前述TLR4基因的4个位点基因型,绘制聚类图,并进行Hardy-Weinberg(H-W)平衡及最小等位基因频率(MAF)检测。采用二分类非条件Logistic回归模型分析上述位点不同基因型与脑梗死发病风险的相关性。以spearman秩相关方法对病例组基因型与发病年龄进行相关性分析。结果两组观察对象4种SNP位点基因聚类图均正常,H-W平衡检验P值和MAF值均大于0.05。rs1927914 A/G基因型频率分布差异有统计学意义(χ~2=9.267,P=0.010),对照组GG频率显著高于病例组。二分类logistic分析显示,rs1927914 GG基因型发生脑梗死风险的概率是AA型的37.7%(校正OR=0.377,95%CI=0.189～0.750,P=0.005);其余SNP位点基因型均未发现差异有统计学意义(均P≥0.05);相关分析结果显示rs11536891基因型与发病年龄存在负相关(r=-0.156,P=0.035)。结论 rs1927914基因位点基因型与缺血性脑卒中发生存在显著关联,rs11536891基因型与缺血性脑卒中的发病年龄存在负相关性。     

2型糖尿病患者基质金属蛋白酶-12基因多态性与缺血性卒中的相关性研究

目的探讨2型糖尿病患者基质金属蛋白酶12(MMP-12)基因多态性与缺血性卒中的相关性。方法选择2013年1月至2015年12月在本科治疗的217例2型糖尿病合并缺血性卒中患者作为病例组,按照TOAST分型结果将病例组患者分为大动脉粥样硬化性卒中(LAA)组88例和非大动脉粥样硬化性卒中(n-LAA)组129例,选择同期在我院体检的无缺血性卒中的2型糖尿病患者100例作为对照组,采用聚合酶链反应-限制性内切酶分析(PCR-RFLP)法比较MMP-12(-82 A/G)和MMP-12(-1082 A/G)基因型多态性在各组间的差异。结果病例组和n-LAA组MMP-12(82 A/G)基因型和等位基因与对照组比较,差异均无统计学意义(P0.05)。LAA组(G/G+A/G)基因型频率显著高于对照组(22.73%vs 11.00%,P=0.031);G等位基因频率也高于对照组(18.18%vs 10.05%,P=0.033)。n-LAA组MMP-12(-1082 A/G)基因型和等位基因与对照组比较,差异均无统计学意义(P0.05)。病例组和LAA组(G/G+A/G)基因型频率均显著高于对照组(33.64%vs 22.00%,P=0.036;37.50%vs 22.00%,P=0.020);两组G等位基因频率也均高于对照组(25.58%vs 17.00%,P=0.017;30.68%vs 17.00%,P=0.002)。多因素Logistic回归分析结果显示MMP-12-82A/G等位基因G和MMP-12-1082A/G等位基因G均是2型糖尿病患者发生LAA的危险因素(OR=1.107,95%CI 1.010-1.371,P=0.031;OR=1.285,95%CI 1.142-1.817,P=0.010)。结论对于2型糖尿病患者,MMP-12基因-82位点G等位基因和-1082位点G基因多态性与大动脉粥样硬化性卒中密切相关。     

MMP-2、MMP-9基因多态性与缺血性脑卒中临床分型及预后

目的探讨基质金属蛋白酶2(Matrix Metalloproteinase-2,MMP-2)基因C1306T、C735T和MMP-9基因C1562T多态性位点与缺血性脑卒中的关系。方法采用限制性片段长度多态性分析技术,检测缺血性脑卒中组232例和健康对照组235例MMP-2基因C1306T、C735T和MMP-9基因C1562T多态的分布。结果缺血性脑卒中组和对照组MMP-2 C1306T基因型和等位基因频率分布无统计学意义。在动脉粥样硬化性血栓性脑梗死组MMP-9 C1562T的CT+TT基因型频率和T等位基因频率、MMP-2 C735T的CC基因型频率和C等位基因频率明显高于对照组(P<0.05),而在脑栓塞组、腔梗组差异无统计学意义(P>0.05)。多因素Logistic回归分析,MMP-2、MMP-9不同基因型别与缺血性脑卒中预后无显著相关性(P>0.05)。结论 MMP-2 C735T的C等位基因、MMP-9 C1562T的T等位基因是动脉粥样硬化性血栓性脑梗死的遗传易感基因之一。MMP-2、MMP-9基因多态性与缺血性脑卒中预后无关。     

ApoE和Slco1B1基因多态性与缺血性脑卒中的相关性分析

目的 探讨汉川市汉族人群ApoE基因和Slco1B基因多态性与缺血性脑卒中的相关性。方法 收集450例缺血性脑卒中患者(实验组)和健康对照人群(对照组)的血液,通过直接测序法分析对照组和实验组人群ApoE和Slco1B1基因型; Hardy-Weinberg平衡定律检测遗传平衡性。结果(1)ApoE基因型频率符合Hardy-Weinberg平衡定律(P=0.982),ApoE基因型可能与缺血性脑卒中有关(P=0.034);(2)Slco1B1基因型频率符合Hardy-Weinberg平衡定律(P=0.469),Slco1B1基因型可能与缺血性脑卒中有关(P=0.031)。结论 汉川市汉族人群ApoE基因和Slco1B1基因多态性可能与缺血性脑卒中有关。     

AGT基因多态性与出血性脑卒中的相关性研究

目的探讨中国汉族人群中AGT基因上的rs2067853和rs4762单核苷酸多态性与出血性脑卒中的相关性。方法研究采用病例-对照研究方式,收集出血性脑卒中患者共255例(ICH组),健康体检者共321例(NC组)。基因分型采用Sequenom飞行时间质谱平台进行检测,χ~2检验分析两组间等位基因和基因型的分布频率是否存在差异,并且按照性别进一步进行分层分析。多因素交互作用的影响采用Logistic多元回归分析。结果 ICH组和对照组rs4762等位基因和基因型分布频率比较差异无统计学意义(均P0.05)。男性中,rs2067853在两组间的基因型分布频率差异有统计学意义,TT基因型是出血性脑卒中的危险因素(P=0.014,OR=9.053);而女性中两组间差异无统计学意义(P0.05)。Logistic回归分析表明携带rs2067853 TT基因型的男性、高血压、血糖、糖化血红蛋白、体质量指数是出血性脑卒中的风险因素。结论rs4762位点多态性与出血性脑卒中易感无关。而rs2067853位点多态性与出血型脑卒中易感的相关性存在性别特异性:与男性出血性脑卒中易感相关,TT是风险因素;与女性出血性脑卒中易感无关。     

P-选择素基因S290N和P-选择素糖蛋白配体-1基因M62I多态性与缺血性脑梗死临床关联性研究

目的探讨P-选择素(SELP)基因S290N和P-选择素糖蛋白配体-1(PSGL-1)基因M62I多态性与缺血性脑梗死的关系。方法选取148例缺血性脑梗死患者作为脑梗死组,并分为大动脉粥样硬化性(LAA)亚组、心源性脑栓塞(CE)亚组和小动脉闭塞性(SAO)亚组;88例正常人群作为正常对照组。运用基因测序方法检测所有受试者SELP基因S290N和PSGL-1基因M62I的基因多态性。结果与正常对照组比较,脑梗死组及其亚组S290N基因型和等位基因频率差异无统计学意义(均P0.05);脑梗死组M62I基因型和等位基因频率差异有统计学意义(均P0.01);LAA亚组M62I基因型差异无统计学意义(χ~2=5.889,P=0.053),但等位基因频率差异有统计学意义(χ~2=6.156,P=0.021);CE亚组基因型和等位基因频率差异均无统计学意义(χ~2=1.693,P=0.429;χ~2=1.372,P=0.238);SAO亚组基因型和等位基因频率差异均有统计学意义(χ~2=12.572,P=0.002;χ~2=8.736,P=0.004)。S290N与缺血性脑梗死风险无相关性(均P0.05)。M62I显性模型和超显性模型与缺血性脑梗死风险有相关性(OR=2.662,95%CI:1.531~4.630,P=0.000;OR=0.392,95%CI:0.219~0.701,P=0.001),而隐性模型和加性模型与缺血性脑梗死风险无相关性(OR=1.428,95%CI:0.528~3.862,P=0.630;OR=2.121,95%CI:0.766~5.872,P=0.156)。结论 PSGL-1基因M62I多态性与缺血性脑梗死之间具有相关性。     

生物钟核心基因多态性与缺血性脑卒中疾病的关联性

目的 探索生物钟分子发条中核心时钟基因单核苷酸多态性ARNTL rs6486122、PER1 rs2253820与缺血性卒中发病的关联性。方法 采用SNaPshot法检测候选SNPs基因型。不同的基因型被当作分类变量,疾病组与对照组间基因型及遗传模型的比较采用Logistic回归分析,并校正年龄、性别、血脂异常、既往病史等相关危险因素,分别计算不同基因型及遗传模型的调整OR值和95%CI。结果 多因素Logistic回归分析显示,随着受试者年龄的增长脑卒中的患病风险显著增加（P<0.001,OR=6.704,95%CI 5.188～8.644）;高血压患者较非高血压患者的患缺血性脑卒中风险增加2.565倍（P<0.001,OR=2.565,95%CI 1.971～3.338）;血脂异常患者较血脂正常人群患缺血性脑卒中的风险增加1.700倍（P=0.001,OR=1.700,95%CI 1.230～2.348）;收缩压及舒张压增高,同样也会增加卒中的患病风险。对于PER1基因rs2253820位点,以野生纯合子TT基因型为参比,CT基因型,CC基因型以及显性遗传模型在增加脑卒...     

缺血性脑卒中CARD8 rs2043211和NLRP3 rs10754558的遗传共关联作用

目的旨在探索Nod样受体蛋白3(nodlike receptor protein 3,NLRP3)炎症小体组分基因胱天蛋白酶募集域蛋白8(caspase recruitment domain-containing protein 8,CARD8)rs2043211及NLRP3 rs10754558的组合多态性是否会影响中国汉族人群缺血性脑卒中的遗传易感性。方法依据改良的急性卒中治疗Org10172试验(trial of org10172 in acute stroke treatment,TOAST)病因分型诊断标准,将动脉粥样硬化血栓型(n=145)及小动脉型(n=89)缺血性脑卒中纳入本研究,收集对照组115例,应用TaqMan MGB RT-PCR技术进行基因分型,以logistic回归分析基因-基因间的交互作用。结果 NLRP3 rs10754558或CARD8 rs2043211单一基因的小等位基因及基因型频率,在脑梗死两个亚组中的分布,与对照组比较均无统计学差异(P0.05);logistic回归分析发现,rs10754558的CG基因型与rs2043211的AT基因型在动脉粥样硬化血栓型缺血性卒中的发病中存在交互作用,并增加发病风险(P0.01,OR=4.95,95%CI:1.69～14.51)。结论NLRP3炎症小体组分基因的基因型组合CARD8 rs2043211/NLRP3 rs10754558 AT/CG是动脉粥样硬化血栓型缺血性脑卒中的危险因素。     

肿瘤坏死因子超家族成员4基因SNP rs3850641与脑梗死

目的 探讨肿瘤坏死因子超家族成员4(TNFSF4)基因SNP rs3850641与湖南地区脑梗死发病风险的关系.方法 采用TaqMan-PCR方法检测TNFSF4基因SNP rs3850641基因型与等位基因频率.湖南藉汉族脑梗死284例,309例匹配的对照组进行关联研究.结果 脑梗死组和对照组各基因型(x2=3.551,P=0.169)和等位基因频率(x2=3.261,P=0.071)组间分布无显著性差异;两种脑梗死亚型与对照组之间基因型和等位基因频率分布无统计学差异(P>0.05);男性CI组G等位基因频率明显低于对照组,有统计学意义(x2=5.993,P<0.05).Logistic多因素回归分析显示rs3850641各基因型没有使脑梗死发病的危险增加.结论 TNFSF4基因SNPrs3850641可能不增加湖南地区脑梗死的发病风险.     

Association of E-selectin gene polymorphisms with ischemic stroke in a Chinese Han population

The E-selectin gene, a member of the selectin superfamily of adhesion molecules, plays an important role in the pathogenesis of thrombovascular diseases. The present study was designed to investigate the potential relationship between E-selectin gene polymorphisms and ischemic stroke in a Chinese Han population. Three hundred fourteen ischemic stroke patients and 389 unrelated healthy controls were recruited for the study. Three single-nucleotide polymorphisms (SNPs)-rs1805193(G98T), rs5361(A561C), and rs5355(C1839T)-in the exon region of the E-selectin gene, were genotyped using a Multiplex SNaPshot sequencing assay. The data showed that the genotype and allele frequencies of G98T and C1839T SNP were similar in both ischemic stroke patients and the controls. In contrast, the frequency of both the AC genotype and the C allele of A561C was significantly higher in ischemic stroke patients than in healthy controls (P = 0.001, P < 0.001, respectively). After adjusting for other risk factors (such as hypertension, diabetes, tobacco smoking, and alcohol consumption), the E-selectin gene AC genotype and C allele of A561C were still associated with a risk of ischemic stroke (odds ratio [OR] = 2.73, 95% confidence interval (CI): 1.29-5.76, P = 0.008; OR = 2.80, 95% CI: 1.58-4.94, P < 0.001, respectively). Our current study demonstrates that the E-selectin SNP A561C is associated with increased risk for the development of ischemic stroke in this subset of the Han Chinese population.     

NADPH氧化酶p22~(phox)亚基基因多态性与急性动脉硬化性脑梗死的关联性研究

目的探讨CYBA基因的多态性位点与急性动脉硬化性脑梗死的相关性。方法收集284例脑梗死患者(脑梗死组)及335例同期健康体检者(对照组),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测CYBA基因rs4673和rs3180279位点的基因型。结果 rs4673位点的基因型及等位基因频率分布在脑梗死组和对照组中差异无统计学意义(P0.05)。脑卒中组男性患者rs3180279位点GC、GG基因型的频率低于对照组,CC基因型的频率高于对照组(P=0.034)。结论 CYBA基因的rs4673位点与中国北方汉族人群的急性动脉硬化性脑梗死无相关性,男性rs3180279位点GG+GC基因型的携带者较CC基因型携带者动脉硬化性脑梗死的发病率可能更低。     

脂联素基因单核苷酸多态rs266729、 rs2241766、rs822396与老年缺血性 脑血管病亚型相关性研究

目的 探讨中国北方青岛地区汉族人群脂联素（adiponectin,ADIPOQ）基因多态性与老年缺血性脑血
管病发病的相关性。
方法 入组年龄大于60岁的老年缺血性脑血管病患者,按急性卒中治疗低分子肝素试验（Trial
of Org 10172 in Acute Stroke Treatment,TOAST）分型,选取大动脉粥样硬化性（large artery
atherosclerosis,LAA）和小动脉闭塞性（small artery occlusion,SAO）两种亚型患者,其中LAA 144例,
SAO 221例;402例同期查体者进行病例对照研究。对比两组的ADIPOQ基因多态性。
结果 rs266729（-11377C/G）的基因型分布在LAA组、SAO组与对照组3组中有显著差异（P =0.036）。
3组中两两比较显示,SAO组中rs266729（-11377C/G）GG基因型分布显著高于对照组（P =0.009）;在
隐性［P =0.004,比值比（odds ratio,OR）=2.478,95%可信区间（confidence interval,CI）=1.31～4.70］、
累加模式（P =0.003,OR 2.680,95%CI 1.39～5.15）下,rs266729（-11377C/G）基因型分布在SAO组与
对照组中也有显著差异,G 等位基因能增加SAO型缺血性脑血管病的风险,但在显性模式下差异无显
著性。rs822396（-3964A/G）、rs2241766（-45T/G）的基因型分布在LAA组、SAO组与对照组3组中均
无显著差异。
结论 rs266729（-11377C/G）G 等位基因与老年缺血性脑血管病发病相关,其G 等位基因变异可增
加老年患者SAO型缺血性脑血管病的风险。     

趋化因子CXCL16基因A181V多态性与TOAST分型的相关性研究

目的 探讨趋化因子CXC配体16（chemokine CXC ligand 16,CXCL16）基因A181V位点多态性与血清CXCL16水平、脑梗死（cerebral infarction,CI）及急性卒中治疗低分子肝素试验病因分型法（the Trial of Org 10172 in Acute Stroke Treatment,TOAST）分型的关系。方法 采用聚合酶链反应-限制性片段长度多态性方法（polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP）检测基因型,同时对脑梗死急性期患者（n=177）和对照组（查体中心老年健康查体者,n=74）应用酶联免疫吸附法（enzyme linked immunosorbent assay,ELISA）检测血清CXCL16水平。结果 CI组血清CXCL16水平明显高于对照组（P<0.001）;按TOAST分型后比较,大动脉粥样硬化性卒中（large artery atherosclerotic stroke,LAA）组、小动脉闭塞性卒中（small artery occlusion stroke,SAO）组及对照组三组之间血清CXCL16水平差异仍有显著统计学意义（P<0.001）;Logistic回归显示血清CXCL16水平是CI的独立危险因素（P<0.001）。CXCL16基因A181V多态性位点基因型频率及等位基因频率在CI组和对照组之间无显著差异（P>0.05）,但是TOAST分型后显示AA纯合子比G等位基因携带者（GA+GG）发生大动脉粥样硬化性卒中的危险增加（P<0.001）。多元线性回归显示,CXCL16基因A181V多态性与血清CXCL16水平独立相关（P=0.009）。结论 CXCL16基因A181V多态性与血清CXCL16水平有关,AA基因型与大动脉粥样硬化性卒中密切相关,A等位基因是大动脉粥样硬化严重程度的重要标志。     

Two Novel SNPs in the PLCL2 Gene Associated with Large Artery Atherosclerotic Stroke Identified by Fine-Mapping

A genome-wide association study (GWAS) reported that the single nucleotide polymorphism (SNP) rs4618210 in the PLCL2 gene is related to myocardial infarction (MI) in the Japanese population, but no study has examined the correlation of PLCL2 with ischemic stroke (IS). The present study was designed to investigate whether the genetic variation in PLCL2 is associated with large artery atherosclerotic (LAA) stroke in a Han Chinese population. Tagging SNPs (tSNPs) of the PLCL2 gene were determined by a fine-mapping strategy and were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 669 LAA stroke patients and 668 healthy controls. A logistic regression model was used to analyze the associations between genetic variation at PLCL2 and the risk of LAA stroke. Two SNPs were significantly associated with the risk of LAA stroke after adjusting for potential confounders: for rs4685423, the AA genotype and CA genotype decreased the risk of LAA stroke compared with the CC genotype (multivariate-adjusted, P = 0.001); for rs4618210, the AA genotype and GA genotype decreased the risk of LAA stroke compared with the GG genotype (multivariate-adjusted, P = 0.007). In addition, haplotype analysis indicated that compared with haplotype TTT, haplotype TAT decreased the risk of LAA stroke in block 2 (adjusted OR, 0.706; 95% CI, 0.550–0.907; P = 0.006). The analysis of SNP–SNP interactions showed that rs4685423 was the most influential contributor to LAA stroke risk. SNPs rs4685423 and rs4618210 in the PLCL2 gene may be related to the risk of LAA stroke in Han Chinese.     

神经肽Y启动子基因多态性与脑梗死TOAST亚型相关性研究

目的 针对脑梗死多因素致病特点,探讨神经肽Y(NPY)启动子基因多态性与脑梗死TOAST分型各亚型的关系. 方法 采用聚合酶链反应(PCR)和基因测序技术,检测549例脑梗死患者NPY启动子基因-399T/C、-883Tgins/del和-602G/T基因型及等位基因,其中大动脉粥样硬化型(LAA)190例,小动脉闭塞型(SAO)260例,心源性栓塞型(CE)60例,其他明确原因型(ODE)29例,原因不明型(UE)10例,并与423例汉族健康体检者对照.Logistic回归分析去除混杂因素影响,分析NPY启动子基因多态性与脑梗死TOAST分型各亚型的相关性. 结果 SAO亚型-399T/C突变基因型CC和等位基因C频率与对照组比较差异均有统计学意义(P=0.046,P=0.010);LAA亚型和SAO亚型高尿酸、高血压、心脏病和DM病史较对照组明显增高,比较差异有统计学意义(P＜0.05);SAO亚型-883Tgins/del缺失突变基因型DD、等位基因D频率与对照组比较差异无统计学意义(P=0.061,P=0.155);-399T/C、-883Tgins/del、-602G/T多态性与LAA亚型、CE亚型、ODE亚型和UE亚型患者均无相关性. 结论 NPY启动子基因-399T/C多态性可能与脑梗死SAO亚型发病存在相关性,高频率等位基因-399C个体可能是SAO亚型重要危险因素.没发现-399T/C、-883Tgins/del、-602G/T基因多态性与LAA亚型、CE亚型、ODE亚型和UE亚型患者有相关性.高尿酸、高血压、心脏病和糖尿病史是LAA亚型和SAO亚型危险因素.     

The role of fibroblast growth factor receptor 4 polymorphisms in the susceptibility and clinical features of ischemic stroke

Some polymorphisms in the fibroblast growth factor receptor 4 gene (FGFR-4) have been correlated with coronary artery disease, however, the role of polymorphisms in the FGFR-4 gene in ischemic stroke remain unknown. A total of 270 patients with ischemic stroke and 297 controls were recruited. Stroke subtype was classified and clinical severity of stroke in patients was evaluated. The polymorphisms in the FGFR-4 were genotyped. There were no significant differences of genotype distributions and allele frequencies of rs145302848C/G and rs147603016G/A between stroke patients and controls (all p > 0.05). However, genotype frequencies and allele frequencies at rs351855G/A (Gly388Arg) were significantly different between stroke patients and controls (both p < 0.001). With the rs351855GG genotype as a reference, the presence of rs351855AA homozygote had a significantly increased risk for stroke (adjusted odds ratio 2.663; 95% confidence interval 1.673–4.229, p < 0.001). The polymorphisms at rs145302848C/G and rs147603016G/A did not influence the susceptibility of stroke in this study. All FGFR-4 polymorphisms were not associated with clinical features such as Trial of Org 10172 in Acute Stroke Treatment subtype or stroke severity as indicated by mean National Institutes of Health Stroke Scale scores. Our study suggests a positive association between FGFR-4 gene polymorphism at rs351855G/A and susceptibility to ischemic stroke.     

基质金属蛋白酶-9/C1562T基因多态性与缺血性脑卒中的关系

目的探讨基质金属蛋白酶-9(MMP-9)启动子基因C1562T多态性与缺血性脑卒中(IS)的关系。方法采用聚合酶链式反应-限制性片段长度多态性分析(PCR-RFLP)法检测114例IS患者(IS组)及80名正常对照者(NC组)MMP-9/C1562T基因型和等位基因频率,分析其与IS发病的相关性。结果IS组与NC组间MMP-9/C1562T基因型及等位基因频率差异无统计学意义(P>0.05)。结论MMP-9/C1562T多态性可能与IS的发病无关。     

Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2)=8.589; P=0.014), C1298C genotype (OR=2.544; P=0.004), and C677C/C1298C compound genotype (OR=3.020; P=0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2)=11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2)=6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/A1298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors.