ATP结合盒转运子1基因多态性与脑梗死的关系

目的　探讨ATP结合盒转运子 1(ATP bindingcassettetransporter 1,ABCA1)基因R2 19K变异与我国脑梗死发病风险的关系。方法　采用病例对照研究 ,对 379例脑梗死患者和 35 1名健康对照组进行研究。采用聚合酶链反应 限制性片段长度多态性方法测定ABCA1基因多态性。结果　在脑梗死患者和对照组ABCA1R2 19K多态性的三种基因型中 ,RK型发生频率最高 ,RR型次之 ,KK型发生频率最低。脑梗死组KK型频率低于对照组 ,RR型频率高于对照组。脑梗死组和对照组的R2 19K变异携带者 (RK KK型 )频率分别为 6 0 7%和 6 8 1% ,差异有显著意义 (P <0 0 5 )。KK基因型高密度脂蛋白 (HDL C)水平明显高于RR型 (P <0 0 1)。多因素Logistic回归分析脑梗死携带者 (RK KK型 )的OR值为 0 6 73(95 %CI 0 4 76～ 0 95 3,P =0 0 2 6 )。结论　ABCA1R2 19K基因多态性产生有益的临床血脂谱 ,对脑梗死具有保护作用 ,可能是脑梗死的低危遗传标记。     

ATP结合盒转运子1R219K基因多态性与阿尔茨海默病相关性研究

目的探讨胆固醇相关基因ABCA1外显子R219K遗传变异对阿尔茨海默病（AD）发病风险及认知功能的影响。方法采用病例对照研究方法测定湖南长沙地区汉族人群104例散发性AD患者以及104名60岁以上认知功能正常者的ABCA1R219K基因多态性。采用SPSS13．0软件进行统计分析。结果两组间RR、RK及KK3种基因型分布差异有统计学意义（Χ^2=8．777,P=0．012）,AD组KK型频率显著低于对照组（Χ^2=5．261,P=0．022）。AD组（RK＋KK）型频率较对照组显著降低（54．8％＆70．2％,P=0．022）。KK型及K等位基因携带者血浆HDL-C、apoA-I水平增高,差异有统计学意义（P〈0．05）。在总体研究人群中,KK型及RK＋KK型携带者的MMSE评分以及WMS评分显著增高（P〈0．05）;进一步按照长时记忆、短时记忆和瞬时记忆3种记忆类型分析,与RR型相比,RK、KK型及RK＋KK型携带者的短时记忆及瞬时记忆得分显著增高（P〈0．05）,而长时记忆得分的比较差异无统计学意义（P〉0．05）。Logistic回归结果表明K等位基因携带是AD发病的独立保护因素。结论ABCA1R219K变异与AD的发病有关,K等位基因携带对血脂及认知功能可能产生有益作用,并对AD的发生可能有一定保护作用。     

ABCA1基因多态性与腔隙性脑梗死的关系

目的探讨三磷酸腺苷（ATP）结合盒子转运子1（ATP-binding cassette transporter1，ABCAl）基因多态性与腔隙性脑梗死（lacunar infarction）的相关性。方法采用病例一对照方法对109例腔隙性脑梗死患者和339例健康对照者进行研究，并用多聚合酶链式反应（PCR）和限制性片段长度多态性测定ABCAl R219K多态性。结果对照组ABCAl R219K基因型的频率为RR32．4％、RK49．6％和KK18．0％；腔隙性脑梗死组基因型的频率为RR27．5％、RK55．1％和KK17．4％。ABCA lR219K基因型和等位基因频率分布在腔隙性脑梗死组与对照组之间差异无显著性（P〉0．05）。结论未发现ABCA lR219K基因多态性与腔隙性脑梗死存在相关关系。     

ABCA1基因R219K多态性与青年缺血性脑卒中的相关性研究

目的 探讨青年缺血性脑卒中与ATP结合盒转运子A1(ABCA1)基因R219K多态性的关系. 方法 用PCR-RFLP技术检测131名青年缺血性脑卒中患者和135名健康对照者ABCA1基因R219K多态性,并测定2组的血脂水平,缺血性脑卒中患者同时应用颈动脉B超检测颈动脉内膜、中膜厚度. 结果 青年缺血性脑卒中患者KK基因型分布明显低于对照组,差异有统计学意义(P<0.05),其K等位基因频率亦较对照组明显降低,差异有统计学意义(P<0.05).KK基因型与青年缺血性脑卒中呈负相关[OR=0.379,95%CI(0.160～0.899)1,RK+KK基因型与青年缺血性脑卒中亦呈负相关[OR=0.563,95%CI(0.337～0.940)].青年缺血性脑卒中患者、对照组中K等位基因携带者和非携带者血浆总胆固醇、三酰甘油、LDL-C、Apo-A、Apo-B水平差异无统计学意义(P>0.05);而携带者HDL-C水平较非携带者增高,差异有统计学意义(P<0.05).青年缺血性脑卒中患者K等位基因携带者和非携带者中吸烟、高血压、糖尿病的比例及体质指数差异无统计学意义(P>0.05),而携带者的颈动脉内膜、中膜厚度较非携带者明显减少,差异有统计学意义(P<0.05). 结论 ABCA1基因R219K多态性与青年缺血性脑卒中的遗传易感性相关,其中K等位基因可能对缺血性脑卒中有保护作用.推测其保护机制为通过升高血浆HDL-C水平起到减缓颈动脉内膜、中膜增厚,避免动脉粥样硬化的作用.     

ABCAlR219K基因多态性与脑梗死合并2型糖尿病的关系

目的探讨ABCA1 R219K基因多态性与脑梗死合并2型糖尿病的关系。方法采用病例对照方法,对279例脑梗死患者和351例健康对照者进行研究。采用多聚酶链式反应（polymerase chain reaction,PCR）和限制性片段长度多态性测定ABCA1 R219K基因多态性。结果脑梗死组合并糖尿病的患者比例高于对照组合并糖尿病的患者比例,合并糖尿病组的TG、TC水平高于无糖尿病组（P〈0．05）。脑梗死与健康对照各组间ABCA1 R219K各个基因型分布频率比较,无显著差异（P〉0．05）。结论ABCA1 R219K基因多态性与脑梗死合并2型糖尿病无明显关系。     

血栓素A2受体基因多态性与脑梗死的相关性研究

目的 探讨上海地区汉族人群血栓素A2 受体(TXA2R)基因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方法对138例脑梗死患者和135例正常老年对照者TXA2R 基因rs768963位点多态性进行分析,计算其基因型频率和等位基因频率.结果 Logistic回归分析结果显示,血压和血糖水平是脑梗死的独立危险因素.脑梗死组与正常老年对照组受试者TXA2R 基因rs768963位点的基因型(TT 基因型、TC 基因型和CC 基因型)和等位基因(T 和C)频率比较,差异均无统计学意义(P >0.05);进一步Logistic回归分析结果显示,TXA2R 基因rs768963位点基因突变与性别、年龄、血脂、血压和血糖水平均无相关性(P > 0.05).结论 TXA2R 基因rs768963位点多态性可能与上海地区汉族人群脑梗死无关.     

TAFI基因编码区C291T的多态性与脑梗死的相关性研究

目的 探讨中国汉族人群中凝血酶激活的纤溶抑制物(TAH)基因编码区C291T的多态性与脑梗死的相关性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测173例脑梗死患者(脑梗死组)和158例健康人(对照组)的TAFI基因编码区C291T多态性的基因型.结果 脑梗死组TAFI基因C291T多态性的CC基因型为53.2%(92/173),T等位基因携带者为46.8%(81/173);而对照组CC基因型为68.4%(108/158),T等位基因携带者为31.6%(50/158),两组之间的差异有统计学意义(χ2=7.952,P=0.005).脑梗死组C、T等位基因频率分别为70.8%(245/346),29.2%(101/346);对照组C、T等位基因频率分别为81.9%(259/316),18.1%(57/316),两组之间的差异有统计学意义(χ2=11.306,P=0.001).结论 TAFI基因编码区C291T的多态性与脑梗死呈显著性相关.     

广东汉族人群缝隙连接蛋白37基因多态性与动脉粥样硬化性脑梗死的关系

目的探讨广东汉族人群缝隙连接蛋白37(Cx37)基因多态性与动脉粥样硬化性脑梗死的关系。方法应用SNaPshot技术,检测250例动脉粥样硬化性脑梗死患者(病例组)和200例健康人(对照组)的Cx37基因rs1764391多态位点的基因型和等位基因频率。结果病例组与对照组Cx37基因的多态位点rs1764391的基因型分布无统计学意义(P=0.217);病例组的T等位基因频率高于对照组(22.4%vs 17.7%,P=0.085);病例组中,TT+CT基因型(T等位基因携带者)的颈总动脉内膜-中膜厚度大于CC基因型,差异有统计学意义(P=0.032)。结论广东汉族人群Cx37基因的多态位点rs1764391与动脉粥样硬化性脑梗死无关,T等位基因增加颈总动脉内膜-中膜厚度。     

血栓素A2受体基因多态性与脑梗死的相关性研究

目的 探讨上海地区汉族居民血栓素A2受体(TXA2R)基因位点单核苷酸多态性与脑梗死的关系.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334例脑梗死患者和135例正常老年对照者TXA2R基因rs768963位点的单核苷酸多态性,计算等位基因的频率分布.结果 在脑梗死组与正常组之间,rs768963位点的基因型(T/T、T/C与C/C)频率分布差异均无统计学意义(P＞0.05),而等位基囚频率(T/C)分布差异有统计学意义(P＜0.05);Logistic回归分析示rs768963位点基囚突变与性别、年龄、血脂、血压、血糖均无关联.结论 TXA2R基因rs768963位点C等位基因可能是脑梗死的危险因素之一,携带C等位基因的患者具有更高的脑梗死发病易感性.     

湖北地区炎症因子基因多态性与动脉粥样硬化性脑梗死的关系

目的探讨相关炎症因子基因多态性与中国湖北地区汉族人群动脉粥样硬化性脑梗死(atherosclerotic cerebral infarction,ACI)的关系。方法在湖北汉族人群中筛选260例脑梗死患者为脑梗死组;200例健康体检者为对照组,采用聚合酶链式反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFIP)方法测定炎症因子基因多态性。结果脑梗死组与对照组比较,BRAP基因外显子90A/G分布存在统计学差异(χ~2=11.2,P0.05),IL-15基因的C/A基因型分布不存在组间统计学差异(χ~2=3.220,P0.05),Logistic回归分析提示,BRAP基因外显子90GG等位基因携带者发生ACI的风险是CC等位基因的1.8倍(OR=1.476,95%CI 1.142~2.268),且该关联独立于性别、年龄、吸烟、高血压等风险因素。没有证据表明IL-15基因13687C/A位点单核苷酸多态性与动脉粥样硬化性脑梗死易感性相关。结论 BRAP 90A/G外显子基因多态性与动脉粥样硬化性脑梗死发病有关,可能是中国湖北地区汉族人群动脉粥样硬化性脑梗死发病的遗传易感基因。     

Decreased frequencies of ABCA1 polymorphisms R219K and V771M in Hungarian patients with cerebrovascular and cardiovascular diseases

BACKGROUND AND PURPOSE: Genetic polymorphisms in ABC transporter A1 (ABCA1) may alter the regulation of plasma high-density lipoprotein (HDL), promoting or protecting from vascular diseases. METHODS: We investigated 244 unrelated, consecutively enrolled patients with ischemic stroke, 150 patients with coronary heart disease (CHD) and 193 blood donors for allele frequencies (AFs) of three common ABCA1 polymorphisms (R219K, V771M and I883M). RESULTS: Compared to controls (30.8 +/- 4.7 and 4.9 +/- 2.2%, respectively), decreased AFs were found in both patient groups for R219K and V771M (28.7 +/- 4.1 and 3.1 +/- 1.6% in stroke, and 25.7 +/- 5.0%; 1.3 +/- 1.3% in CHD patients, respectively). In a subset of stroke patients younger than 50, both variants occurred in significantly lower frequencies (22.4 +/- 5.5 and 1.8 +/- 1.7%, respectively). Similarly, among CHD patients younger than 60, AFs of R219K and V771M (22.6 +/- 7.5 and 0 +/- 1.6%, respectively) were decreased. V771M was almost exclusively (35/36) found in individuals carrying the R219K allele. CONCLUSIONS: Our data confirm earlier observations that ABCA1 R219K and V771M polymorphisms may be associated with a protective role against CHD and extend those to another important pathologic condition, namely stroke.     

Human serum paraoxonase gene polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population

OBJECTIVES: It has been reported that human serum paraoxonase (PON1) gene is associated with coronary heart disease (CHD) and diabetes mellitus (DM). However, little is known about the role of PON1 gene polymorphism in cerebral infarction (CI). For this, we have investigated the relationship between PON1 gene polymorphisms, Q192R and L55M, and CI in Chinese Han population. METHODS: The PON1 genotypes, Q192R and L55M, from 153 CI patients and 153 healthy individuals, were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Their allele frequencies were then determined. The association of the PON1 gene polymorphism with the risk of CI was analysed by statistical analysis software. RESULTS: The frequencies of PON1-Q192R genotypes in CI and control group are 13.7 and 9.8% (QQ), 51.6 and 53.6% (QR), 34.6 and 36.6% (RR) respectively. There is no significant difference in PON1-Q192R genotype (p=0.566) and allele frequencies (p=0.505) between CI patients and controls. The frequencies of PON1-55 genotypes in the CI and control group are 96.7 and 93.5% (LL), 3.3 and 6.5% (LM) respectively. No MM genotype was found in both CI and control group. No significant difference in genotype (p=0.289) and allele (p=0.296) distribution between CI patients and controls was observed. DISCUSSION: Our results suggest that the human serum paraoxonase polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population.     

ABCB1基因多态性与中国汉族人群动脉粥样硬化性血栓性脑梗死的相关性研究

目的探讨ATP结合盒B亚家族成员1转运蛋白(ABCB1)基因多态性与中国汉族人群动脉粥样硬化性血栓性脑梗死(ATCI)患者的关系。方法选取392例ATCI患者(脑梗死组)和429例健康对照者(对照组),通过SNa Pshot方法对ABCB1基因的rs1128503和rs1045642位点进行SNP检测。比较两组的基因型和等位基因分布频率,分析基因型与临床表型的关系。结果脑梗死组rs1128503和rs1045642位点的基因型及等位基因分布频率与对照组比较,无统计学意义(P0.05)。女性ATCI患者的rs1128503位点TT基因型和CC基因型体重指数高于TC基因型(P=0.007,P=0.011)。女性ATCI患者的rs1045642位点CC基因型低密度脂蛋白-胆固醇水平高于CT基因型(P=0.030)。结论 ABCB1基因多态性与中国汉族人群ATCI的发病无明显相关性。rs1128503位点多态性可能与女性ATCI患者的体重指数有关,rs1045642位点多态性可能与女性ATCI患者的低密度脂蛋白-胆固醇水平有关。     

北方汉族人PLA2R1基因多态性与脑梗死关系的研究

目的探讨中国北方汉族人群PLA2R1基因多态性与脑梗死的关系。方法选取年龄、性别匹配的中国北方汉族脑梗死患者212人,健康对照组179人,采用PCR技术和限制性内切酶片段长度多态性(RFLP)的方法检测基因型。结果PLA2R1基因SNP的等位基因和基因型在脑梗死组和对照组的频数分布差异无显著性(P>0.05)。结论中国北方汉族人群中PLA2R1基因多态性与脑梗死的发病可能无关。     

Human serum paraoxonase gene polymorphisms,Q192R and L55M,are not associated with the risk of cerebral infarction in Chinese Han population

Abstract

Objectives: It has been reported that human serum paraoxonase (PON1) gene is associated with coronary heart disease (CHD) and diabetes mellitus (DM). However, little is known about the role of PON1 gene polymorphism in cerebral infarction (CI). For this, we have investigated the relationship between PON1 gene polymorphisms, Q192R and L55M, and CI in Chinese Han population.

Methods: The PON1 genotypes, Q192R and L55M, from 153 CI patients and 153 healthy individuals, were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Their allele frequencies were then determined. The association of the PON1 gene polymorphism with the risk of CI was analysed by statistical analysis software.

Results: The frequencies of PON1-Q192R genotypes in CI and control group are 13.7 and 9.8% (QQ), 51.6 and 53.6% (QR), 34.6 and 36.6% (RR) respectively. There is no significant difference in PON1-Q192R genotype (p=0.566) and allele frequencies (p=0.505) between CI patients and controls. The frequencies of PON1-55 genotypes in the CI and control group are 96.7 and 93.5% (LL), 3.3 and 6.5% (LM) respectively. No MM genotype was found in both CI and control group. No significant difference in genotype (p=0.289) and allele (p=0.296) distribution between CI patients and controls was observed.

Discussion: Our results suggest that the human serum paraoxonase polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population.     

昆明地区汉族人vWF基因多态性与急性脑梗死的相关性

目的 探讨血浆血管性假性血友病因子(von Willebrand factor vWF)表达水平及其基因19内含子MspI(Major surface protease I)多态性与急性脑梗死的相关性.阐明vWF基因19内含子MspI多态性在昆明地区汉族人群中的分布.方法 收集119例急性脑梗死(24 h内)和117名昆明地区汉族健康人为对照,免疫比浊法检测血浆vWF 表达水平;聚合酶链反应-限制性片段长度多态性结合MspI酶切技术进行vWF基因19内含子MspI多态性分析.结果 急性脑梗死血浆vWF表达水平为(189.37% ± 89.55%)明显高于对照组(P ＜ 0.05).昆明地区汉族人群中vWF基因19内含子MspⅠM+/M+、M+/M-和 M-/M-基因型频率分布分别为0.047、0.377和0.576;M+/M-等位基因型频率分布分别为0.235、0.765.脑梗死组MspⅠ多态性M-/M-基因型频率高于对照组(P ＜ 0.05).脑梗死组M+/M+、M+/M-和M-/M-型的循环vWF 水平分别为(170.00% ± 78.67%)、(148.62% ± 62.58%)和(205.38% ± 92.68%),各基因型之间差异有统计学意义(P ﹤0.05).结论 血浆vWF表达水平及vWF 基因19 内含子MspⅠ多态性M-/M-基因型与急性脑梗死发生有显著相关性;昆明地区汉族人群中vWF基因19内含子MspⅠ等位基因M+和M-的分布与其他人群不同.