载脂蛋白E基因多态性与动脉粥样硬化性脑梗死的相关性

目的 探讨载脂蛋白E(ApoE)基因多态性与动脉粥样硬化性脑梗死(ACI)的相关性.方法 运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测92例ACI患者(<60岁42例,≥60岁50例)和50名性别年龄相匹配的正常对照者的ApoE基因型,并进行比较. 结果 ApoE 3/4基因型频率和ε4等位基因频率ACI组为30.4%和19.6%,正常对照组为2%和3%,两组比较差异有统计学意义(均P<0.05).ACI<60岁组和≥60岁组间,ApoE基因型频率和等位基因频率差异无统计学意义.结论 ApoE基因多态性与ACI发病相关,ε4等位基因可能是ACI的易感基因之一.     

PPARγ基因多态性与动脉粥样硬化性脑梗死的相关性研究

目的 探讨PPARγ基因多态性与动脉粥样硬化性脑梗死的关系.方法 本研究共纳入227例动脉粥样硬化性脑梗死患者和404例健康对照人群.以rs1875796为遗传标记,应用多聚酶链-限制性片段长度多态性(PCR-RFLP)技术检测PPARγ基因rs1875796的个体基因型.结果 女性动脉粥样硬化性脑梗死组rs1875796的C等位基因频率较对照组明显增高(χ~2=9.113,P=0.003,OR=2.211,95%CI 1.321～3.700),女性动脉粥样硬化性脑梗死rsl875796位点的CC+CT基因型频率较对照组明显增高(χ=8.032,P=0.005,OR=2.404,95%CI 1.310～4.411),经过多因素回归分析调整了传统危险因素的影响,两组间仍有显著性差异(P=0.006).而男性动脉粥样硬化性脑梗死组与对照组rs1875796的等位基因、基因型频率差异无显著意义.结论 PPARγ基因可能与女性动脉粥样硬化性脑梗死相关.

Abstract：

Objective To investigate the genetic association between the PPARγ gene and atherosclerotic cerebral infarction. Methods 227 patients with atherosclerotic cerebral infarction were recruited into this study, and 404 healthy people were as controls. SNP rs1875796,a C to T base change located in intron 4 of the gene,was used as a genetic marker. PCR-based restriction fragment length polymorphism analysis was applied to genotype rs 1875796 ( Hha I site). Results The frequcncy of allele C was significantly higher in female patients than controls(χ~2 =9. 113,P =0. 003,OR =2.211,95% CI 1. 321～3.700). And the frequcncy of genotype CC + CT was also significantly higher in female patients than controls(χ~2 = 8.032,P = 0.005,OR =2.404, 95% CI 1.310～4.411). Multiple factor regression analysis showed that the differences was still significant after adjusting the traditional risk factors of atherosclerotic cerebral infarction. The frequency of allele C,and genotype CC + CT showed no significance between male patients and controls. Conclusions The present study suggests that the PPARγ gene is likely to contribute to the etiology of atherosclerotic cerebral infarction in female Chinese.     

PON1 Q192R基因多态性与动脉粥样硬化性脑梗死的关系

人血清对氧磷酶（paraoxonase，PON1）相对分子质量约43000，是一种含有三条糖链的Ca^2＋依赖性糖蛋白，它与载脂蛋白AI、载脂蛋白J紧密结合，共同参与高密度脂蛋白的构成。我们对PON1基因编码区Q192R单核苷酸多态性与动脉粥样硬化性脑梗死关系做一探讨，为预防和治疗动脉粥样硬化性脑梗死提供思路。     

载脂蛋白E基因多态性与年轻人动脉粥样硬化性脑梗死关系的研究

ApoE等位基因ε4是动脉粥样硬化(AS)和早发冠心病的显著遗传易感性因子[1,2] .我们分析了ApoE 等位基因在年轻动脉粥样硬化性脑梗死(ACI)患者与正常年轻人群中的分布,探讨其在年轻脑梗死发病中的意义.     

载脂蛋白(a)基因增强子DH Ⅲ多态性与湖南地区汉族人群动脉粥样硬化血栓性脑梗死的相关性

目的研究载脂蛋白(a)基因DHⅢ增强子-1230A/G多态性与湖南地区汉族人群动脉粥样硬化血栓性脑梗死的关系。方法应用聚合酶链式反应-限制性片段长度多态性技术及DNA序列测定法检测湖南地区汉族人群134例动脉粥样硬化血栓性脑梗死患者、110名健康对照者的载脂蛋白(a)基因DHⅢ增强子-1230A/G多态,同时用免疫比浊法检测所有研究对象的血浆脂蛋白(a)水平。结果在动脉粥样硬化血栓性脑梗死组载脂蛋白(a)基因DHⅢ增强子-1230 A/G多态G等位基因频率(0.728)明显高于对照组(0.618;P=0.01);GG型频率(0.500)明显高于对照组(0.400;P0.05)。动脉粥样硬化血栓性脑梗死组各基因型血浆脂蛋白(a)水平均明显高于对照组,差异具有统计学意义(P0.05)。结论载脂蛋白(a)基因DHⅢ增强子-1230 A/G多态性可能与中国湖南地区汉族人群动脉粥样硬化血栓性脑梗死有关;G等位基因可能是动脉粥样硬化血栓性脑梗死的危险因素之一。     

广东汉族人群Toll样受体4基因多态性与颅内外动脉粥样硬化及脑梗死的关系

目的 探讨广东汉族人群Toll样受体4(TLR4)基因A299G和C399T多态性与颅内外动脉粥样硬化及脑梗死的关系.方法 住院及门诊的广东汉族患者200例,根据临床表现、头颅影像学、全脑血管造影、颈动脉彩超或经颅多普勒超声(TCD)检查结果及伴有的脑卒中危险因素分为5组,(1)脑梗死并颅内外动脉粥样硬化性狭窄组(40例),(2)脑梗死无颅内外动脉粥样硬化性狭窄组(40例),(3)颅内外动脉粥样硬化性狭窄而无脑梗死组(40例),(4)有≥3种脑血管病危险因素而无颅内外动脉粥样硬化性狭窄及脑梗死组(40例),(5)正常对照组(40例).采用DNA测序法检测各组TLR4基因中A299G和C399T的基因型和等位基因频率.结果 各组均未见TLR4基因中A299G和C399T多态性的存在.结论 广东汉族人群TLR4基因A299G和C399T多态性可能与颅内外动脉粥样硬化及脑梗死无相关性.     

血清对氧磷酯酶-1活性及其基因多态性与动脉粥样硬化性血栓性脑梗死关系的研究

目的研究中国汉族人血清对氧磷酯酶-1(PON1)活性及PON1Q/R192基因多态性与动脉粥样硬化性血栓性脑梗死(ATCI)的关系。方法采用紫外线分光光度法和聚合酶链式反应-限制性片段长度多态性(PCR-RELP)方法,检测48例ATCI患者和55名相匹配的健康人血清PON1活性及PON1Q/R192基因多态性。结果ATCI组血清PON1活性为(74.41±18.85)U/ml,明显低于健康对照组[(113.65±26.64)U/ml](P<0.05)。ATCI组与健康对照组等位基因频率分别为Q:37%及43%;R:63%及57%,两组间等位基因频率及3种基因型分布差异无统计学意义。结论血清PON1活性降低是ATCI的危险因素之一;PON1Q/R192基因多态性与中国汉族人ATCI的发生无相关性。     

对氧磷酯酶-1与动脉粥样硬化性血栓性脑梗死的关系

目的研究中国汉族人对氧磷酯酶-1(PON1)活性及PON1Q/R192基因多态性与动脉粥样硬化性血栓性脑梗死(ATCI)发病的关系.方法采用紫外分光光度法和PCR-RELP方法检测48例ATCI患者和55例相匹配的健康人血清PON1活性及PON1Q/R192基因多态性,同时测定血脂、血糖等指标,并进行统计学分析.结果 ATCI组血清PON1活性为(74.41±18.85)μg/ml,低于对照组[(113.65±26.64)μg/ml,P＜0.05];ATCI组与对照组等位基因频率分别为Q:37%、43%;R:63%、57%,2组间比较差异无显著性,2组间3种基因型的分布差异也无显著性.结论血清PON1活性降低可能是ATCI的独立危险因素,而PON1Q/R192基因多态性与中国汉族人ATCI的发生无关.     

长沙地区汉族人群apoB基因多态性与脑梗死的关系研究

目的探讨湖南长沙地区汉族人群载脂蛋白B(apolipoprotein B,apoB)G12669A、C7673T多态性与脑梗死的关系。方法采用聚合酶链反应-限制性片段长度多态性分析法分别检测130例脑梗死患者和100例正常对照的apoB基因G12669A、C7673T多态等位基因频率。结果湖南长沙地区汉族人群存在apoB基因G12669A、C7673T多态性,脑梗死组中apoB基因G12669A、C7673T多态等位基因频率G/A为0.904/0.096,C/T为0.881/0.119,在正常对照G/A为0.955/0.045,C/T为0.960/0.040;脑梗死组apoB基因G12669A多态A等位基因频率及C7673T多态T等位基因频率均显高于正常对照组(P<0.05,P<0.01)。结论apoB G12669A多态A等位基因可能是湖南长沙地区汉族人群脑梗死发病的遗传易感因素。     

ABCG1基因多态性与中国汉族人群缺血性脑卒中的相关性研究

目的探讨ATP结合盒G亚组成员1(ABCG1)的基因多态性与缺血性脑卒中的相关性。方法采用病例-对照方法,在中国北方汉族人群中收集389例缺血性脑卒中患者(病例组)与380名正常体检者(对照组)进行对照研究。按改良的TOAST分型将病例组分为动脉粥样硬化血栓形成型亚组(207例)和小动脉闭塞型亚组(182例),采用聚合酶链式反应-连接酶检测方法测定ABCG1基因rs225374位点的多态性。结果在动脉粥样硬化血栓形成型亚组,rs225374位点GG基因型和G等位基因分布频率显著高于对照组(25.6%vs 17.9%,P=0.030;49.8%vs 43.4%,P=0.037);小动脉闭塞型亚组与对照组比较,rs225374位点的基因型和等位基因分布频率差异无显著性。结论 ABCG1基因rs225374位点的多态性与中国北方汉族人群动脉粥样硬化血栓形成性缺血性脑卒中的发病具有一定相关性。     

动脉粥样硬化性脑梗死患者载脂蛋白B基因多态性与血脂水平分析

研究中国动脉粥样硬化性脑梗死（ACI）患者和正常人载脂蛋白B（apoB）基因XbaI和EcoRI两位点多态性与血脂水平的关系。方法采用聚合酶链式反应技术检测了85例ACI患者及56例正常人（NC）的apoB基因多态性。结果（1）NC组X-X 基因型血浆TC水平明显高于X－X－基因型（P＜0．001）;ACI组与NC组少见E＋E－或E－E－基因型,血浆TG水平明显高于E＋E＋基因型（P＜0．02）。（2）X－X－基因型个体：ACI组血浆TC、TG、apoB、Lp（a）水平明显高于NC组,apoA水平明显低于NC组。（3）ACI组EcoRI位点不同基因型个体TC、TG水平均明显高于NC组,而apoA水平明显低于NC组。结论呈X－X－基因型患者可能与ACI患者血脂异常有关,apoB基因多态性对血浆TC、TG水平影响较大。     

对氧磷脂酶1基因多态性与脑梗死的相关性研究

目的：探讨对氧磷脂酶1（PON1）基因的标签位点（tagSNP）rs854552多态性与脑梗死的相关性。方法：缺血性脑卒中患者按TOAST分型标准分为动脉粥样硬化性脑梗死组393例、腔隙性脑梗死组292例和健康对照组431名。以位于PON1基因的rs854552位点为遗传标记,应用聚合酶链法（PCR）和限制性片段长度多态性法（RFLP）检测PON1基因的多态性。结果：动脉粥样硬化性脑梗死组和腔隙性脑梗死组的PON1基因型及等位基因频率与对照组比差异无统计学意义（P〉0．05）。经性别分层后也未见显著差异。结论：PON1基因（tag SNP）rs854552可能与动脉硬化性脑梗死的发病无关。     

A Preliminary Study of the Association between Apolipoprotein E Promoter Methylation and Atherosclerotic Cerebral Infarction

Aim: To investigate association of Apolipoprotein E (ApoE) gene promoter methylation with atherosclerotic cerebral infarction (ACI) in the Han Chinese population. Methods: Twenty-six ACI patients (the case group) and 26 healthy (the control group) were recruited randomly from Henan Han nationality population, from April 2016 to August 2016. Bisulfite pyrosequencing technology was used to examine the role of the aberrant gene promoter methylation in ACI in Han Chinese population. Especially, we used the odds ratio and 95% confidence interval (95% CI) method to elevate the correlation between ApoE Promoter Methylation and ACI. Results: The case group was significantly more likely to have hypertension and carotid atherosclerotic plaques (Table 1). The case group had significantly lower levels of high-density lipoprotein cholesterol (HDL-C), folate, and higher levels of homocysteine (Table 2). We observed that ACI patients (n?=?26) had significantly higher methylation levels at cytosine-phosphate-guanine (CpG) 14 and CpG16 compared with controls (n?=?26) (Table 3). Importantly, our results indicated a significant association between ApoE promoter methylation and ACI (OR?=?16.146; 95% CI, 1.154-225.832; P* < .05; P*: adjusted for age, gender, carotid atherosclerotic plaque, hypertension, HDL-C, homocysteine, and folate) (Table 4). Conclusions: Our study indicates that ApoE promoter methylation may be associated with ACI in Han Chinese people.     

TAFI基因编码区的单核苷酸多态性与脑梗死的相关性探讨

目的　凝血酶激活的纤溶抑制物 (Thrombinactivatablefibrinolysisinhibitor ,TAFI)具有抑制纤维蛋白溶解的功能 ,它在止血中起重要的作用。TAFI的血浆浓度是受TAFI基因变异调节的 ,因此TAFI基因可能是脑梗死的候选基因之一。探讨TAFI基因单核苷酸的多态性与脑梗死的关系。方法　收集了 189例尸体检查的样本 ,其中包括 95例脑梗死和 94例的对照组。TAFI基因G5 0 5A和C10 4 0T的基因型是用PCR -RFLP(Restrictionfragmentlengthpolymorphism)法来分析。 结果　G5 0 5AandC10 4 0T的基因型频率分布是A5 0 5A 12 (6 % ) ,G5 0 5A 75 (4 0 % ) ,G5 0 5G 10 2 (5 4 % ) ;C10 4 0C 139(74 % ) ,C10 4 0T 4 5 (2 3% ) ,T10 4 0T 5 (3% )。在脑梗死组和对照组之间 ,这些基因型的分布没有显著性差别 (P >0 .0 5 )。结论　TAFI基因单核苷酸的多态性 (G5 0 5A和C10 4 0T)与脑梗死没有显著性相关。     

基质金属蛋白酶9基因多态性与脑梗死的关系研究

目的：探讨基质金属蛋白酶9（MMP-9）启动子区C-1562T的基因多态性与脑梗死的关系。方法：用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测224例脑梗死患者（脑梗死组）和112例同期健康体检者（对照组）的MMP-9启动子区的1562C/T的基因多态性,并进行基因测序,检测MMP-9C-1562T的基因型。结果：脑梗死组MMP-9基因的1562C/T的基因多态性出现频率（16.96%）与对照组（17.86%）无明显差异。结论：MMP-9基因C-1562T的基因多态性与脑梗死无相关性。     

Association Between Osteopontin Gene Polymorphisms and Cerebral Palsy in a Chinese Population

Cerebral palsy (CP) is a neurological disorder affecting movement and posture that develops as a complication of prenatal, perinatal, and postnatal brain injury. Such non-progressive brain injury is often accompanied by neonatal encephalopathy and inflammation. The widely expressed soluble cytokine osteopontin (OPN) plays an important role in inflammation and neurological protection. Therefore, it is of great interest to study the relationship between CP and genetic variants of OPN. To explore the genetic association between OPN gene single nucleotide polymorphisms (SNPs) and CP in the Chinese Han population, five SNPs (rs2853744, rs2853749, rs11728697, rs4754, and rs1126616) were genotyped among 715 CP patients and 658 healthy controls using the MassArray platform. Statistical analysis was performed using the online SHEsis program, and Bonferroni correction was applied as necessary. We found an association between rs1126616 and global CP (corrected allelic P = 0.0006 and genotypic P = 0.0011 after Bonferroni correction). The other SNPs were not statistically associated with CP or any of its subgroups. By testing a relatively large sample size, our study demonstrates that the OPN gene SNP rs1126616 is statistically associated with CP. We suspect that the OPN gene might be a susceptibility factor for CP.     

血管紧张素原基因T704C多态性及血脂水平与动脉硬化性脑梗死的相关性研究

目的探讨血管紧张素原∽G7）基因T704C多态性与血脂水平及动脉硬化性脑梗死（ACI）的关系。方法2206为离退休职工为研究对象,进行体格检查和问卷调查,资料完整者l990名入选,其中男性1289名、女性701名。1990名中共检出ACl患者170例（男性132例,女性38例）为ACI组;余1820名无ACT者（男性1155例,女性665例）为对照组。采用PCR-RFLP方法检测AGT基因T704C基因型,采用全自动生化分析仪测定血脂等生化项目。结果ACI组性别、年龄、平均收缩压、平均舒张压、体重指数、血糖与对照组比较,两组问差异有统计学意义（P〈O．05）;调查人群中,携带AGT基因CC基因型的人群中,ACI患病率高干携带TT、TC基因型者（P〈0．05）;且携带C等位基因的人群ACI患病率高于携带T等位基因的人群（P〈0．05）;两组间血脂水平比较,对照组携带TC、CC基因型者高密度脂蛋白水平高于ACI组（P〈0．05）;携带CC基因型者三酰甘油水平明显低于ACI组（P〈0．05）。结论AGT基因T704C多态性及血脂水平与ACI相关。     

动脉硬化性大脑中动脉狭窄或闭塞所致脑梗死类型

目的探讨动脉硬化性大脑中动脉狭窄或闭塞性疾病(MCAOD)所致脑梗死的类型。方法对50例经颅脑MRA或DSA确诊的症状性MCAOD患者进行研究,依据其头部弥散加权成像(DWI)和T2W的改变对脑梗死分型。结果50例患者共发现57条动脉硬化性大脑中动脉狭窄或闭塞,未发现病灶的有6(占12．0%)个大脑半球,多发性脑梗死和单发脑梗死分别见于13(占22．8%)个和38(占66．7%)个大脑半球。脑分水岭梗死、流域性脑梗死、半卵圆区脑梗死、多发性散在点状脑梗死(MSSI)、腔隙性脑梗死分别见于18(占31．6%)个、12(占21．1%)个、6(占10．5%)个、2(占3．5%)个和1(占1．8%)个大脑半球。结论MCAOD可引起各种类型的脑梗死,脑分水岭梗死约占1/3,动脉粥样硬化性血栓形成约占1/5,纹状体内囊梗死约占1/5,主要发病机制与动脉-动脉栓塞和低灌注有关。     

Association Between VKORC1 Gene Polymorphisms and Ischemic Cerebrovascular Disease in Chinese Han Population

The vitamin K epoxide reductase subunit 1 gene (VKORC1) plays a key role in vitamin K recycling, and there is a close association between VKORC1 gene single-nucleotide polymorphisms (SNPs) and the required dose of warfarin, an anticoagulant. However, the association between VKORC1 SNPs and ischemic cerebrovascular disease (ICVD) has not been defined. This case–control study involved 370 patients with ICVD and 408 healthy individuals (controls) from Chinese Han population. Two VKORC1 gene SNPs (1639A/G and 1173T/C) were genotyped by PCR-RFLP method. The G allele frequencies of the 1639A/G locus and C allele frequencies of the 1173T/C locus were higher in the ICVD group than in the control group (p?=?0.014 and p?=?0.008, respectively). Haplotype analysis showed that 1639G-1173C was associated with an increased risk of ICVD (odds ratio (OR)?=?1.163, 95 % confidence interval (CI)?=?1.137~2.288), while 1639A-1173T was associated with decreased risk of ICVD (OR?=?0.620, 95 % CI?=?0.437~0.880). Our findings suggested that individuals carrying the 1639G or 1173C allele might be at increased risk for ICVD. Furthermore, the 1639G-1173C haplotype was a risk factor for ICVD, and 1639A-1173T was a protective factor in Chinese Han population.