血清sICAM-1水平及ICAM-1基因K469E多态性与脑小血管病关系研究

目的探讨血清sICAM-1水平及ICAM-1基因K469E多态性与脑小血管病之间的关系。方法选择脑小血管病(CSVD)患者158例为病例组,选择健康体检者150例为对照组。利用ELISA法检测两组血清sICAM-1水平,并对比分析;利用PCR-RFLP法对两组ICAM-1基因K469E多态性位点进行检测和分析。结果 (1) CSVD组sICAM-1血清水平明显高于对照组(P 0. 001);(2) CSVD组EE基因型和E等位基因频率明显高于对照组(χ~2=6. 435,P=0. 011;χ~2=9. 049,P=0. 003)。Logistic回归分析校正后,CSVD组与对照组之间ICAM-1基因EE型分布差异仍有统计学意义(OR=2. 649,P=0. 014)。结论血清sICAM-1可以作为CSVD的生物学标志物; ICAM-1 K469E基因EE基因型与CSVD具有相关性,提示ICAM-1 K469E基因多态性可能是CSVD发病的遗传学危险因素。     

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。     

广州市阿尔茨海默病人及正常老人丁酰胆碱酯酶基因K变异对照研究

目的　观察丁酰胆碱酯酶基因 (BCHE)K变异在广州地区汉族老年人中的分布 ,探讨其与晚发阿尔茨海默病 (AD)的关联性。方法　以 10 6例晚发AD患者和 133名健康老年人为对象进行病例 对照研究。采用等位基因特异聚合酶链反应法 (AS PCR)分析BCHE基因K型多态性。结果　晚发AD患者和正常老年人中 ,正常等位基因 1的频率分别为 93 4 0 %和 93 6 1% ,K变异等位基因 2的频率分别为 6 6 0 %和 6 39% ;晚发AD患者和正常老年人之间BCHE基因K多态各等位基因和基因型分布差异无显著性 (P >0 0 5 ) ;样本采用载脂蛋白Eε4基因 (APOEε4 )分层后 ,AD组与对照组BCHE基因K变异频率仍然无显著性差异 (P >0 0 5 )。结论　BEHE K变异在广州地区汉族人群中与晚发AD不存在关联 ,提示该多态性不是晚发AD的风险因子。     

心血管危险因子与广西汉族迟发性阿尔茨海默病之间的相关性研究

目的　研究心血管危险因子载脂蛋白 E( Apo E)、载脂蛋白 C- ( Apo C- )以及低密度脂蛋白受体相关蛋白 ( LRP)与汉族迟发性阿尔茨海默病 ( LOAD)之间的相关性。方法　应用 PCR-RFLP技术或直接通过 PCR方法 ,分析了 1 5 6例正常老年人、79例 LOAD Apo E、Apo C- 与 LRP基因型。结果　在 LOAD患者组和正常对照组中 ,Apo Eε4等位基因出现的频率分别为 1 7.7%、5 .7% ,其间差异有显著性 ( x2 =1 5 .75 0 ;P=0 .0 0 1 ,OR=3 .3 96,95 % CI =1 .80 8～ 6.3 79) ;Apo Eε3等位基因频率分别为 76.0 %、84% ,前者低于后者 ( x2 =4.43 9;P=0 .0 3 5 ,OR=1 .65 9,95 % CI =1 .0 3 3～ 2 .665 ) ;LRP、Apo C- 基因的基因型频率和等位基因频率在 LOAD与对照组之间差异无显著性 ( P >0 .0 5 )。结论　 Apo Eε4等位基因是 LOAD的遗传危险因子 ,Apo Eε3等位基因则可能有保护效应 ;此研究未能证明 Apo C- 基因变异和 LRP基因 C766T多态性与 LOAD有相关关系     

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。     

载脂蛋白E基因多态性与Alzheimer病和血管性痴呆的关系

目的 探讨载脂蛋白E(ApoE)基因多态性与Alzheimer病(AD)和血管性痴呆(VD)的关系.方法 用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测79例AD患者(AD组)、85例VD患者(VD组)及156名健康老年人(正常对照组)ApoE基因型和等位基因频率.结果 ApoEε3/ε4基因型及ε4等位基因频率AD组分别为25.3%及17.7%,VD组分别为25.9%及20.5%,正常对照组分别为10.9%及5.7%;AD组及VD组ApoEε3/ε4基因型及ε4等位基因频率显著高于正常对照组(均P＜0.01).结论 ApoEε4等位基因可能是AD和VD共同的危险因素.     

胰岛素样生长因子1、载脂蛋白酶E基因多态性与阿尔茨海默病关系的研究

目的探讨河南省汉族人群胰岛素样生长因子1(insulin like growth factor 1,IGF-1)基因rs972936位点多态性、载脂蛋白酶E(Apo E)基因多态性与阿尔茨海默病(Alzheimer’s disease,AD)之间的相关性。方法选取58例AD患者和126例年龄、性别相匹配的健康对照(ND)者为研究对象,柱层析法提取外周血基因组DNA,采用PCR和基因测序技术检测IGF-1基因rs972936位点及Apo E基因型多态分布,并进行对比分析。结果与ND组比较,AD组IGF-1基因rs972936位点3种基因型分布总体差异有统计学意义(χ~2=6.108,P=0.047),其中AD组中GG基因型的频率高于对照组(70.7%51.6%,χ~2=5.935,P=0.015),G等位基因频率明显高于健康对照组(χ~2=6.502,P=0.011);AD组Apo Eε4等位基因频率可能增加AD的患病风险(OR=2.872,95%CI 1.542~5.351)(P=0.001);Apo Eε4等位基因不影响IGF-1基因rs972936位点的基因型或等位基因的分布频率(P0.05)。结论 IGF-1基因rs972936位点多态性与河南汉族人群AD的发病可能有相关性,其中GG基因型、G等位基因可能是AD发病的独立于Apo Eε4等位基因的危险因素。Apo Eε4等位基因是散发性AD的主要危险因素。     

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.     

雌激素受体基因多态性与多发性硬化

目的　探讨雌激素受体 ( ER)基因多态性与多发性硬化 ( MS)的相关性。方法　应用限制性片段长度多态性聚合酶链反应 ( RFLP-PCR)分析方法 ,检测 63例 MS患者和 95例对照者 ER基因 Pvu 和 Xba 酶切多态性。结果　MS组 P等位基因频率明显高于对照组 ( P=0 .0 2 2 ,OR=1 .70 8,95 % CI:1 .0 78～ 2 .70 5 ) ,且在女性 MS患者 P等位基因分布频率和对照组间差异有显著性 ( P =0 .0 48,OR =1 .82 4,95 % CI :1 .0 0 3～ 3 .3 1 8)。MS组 Ppxx基因型频率明显高于对照组 ( P =0 .0 0 6)。结论　ER基因 Pvu 酶切多态性与 MS存在相关性 ,可能是 MS发病的危险因素之一 ,尤其是携带 P等位基因的女性更易患 MS;Xba 酶切多态性与 MS无相关性     

Intercellular adhesion molecule-1 gene polymorphism in Iranian patients with multiple sclerosis

Intercellular adhesion molecule-1 (ICAM-1), an important molecule in leucocyte activation and migration, is expressed on the CNS endothelial cells of patients with multiple sclerosis. This study was conducted to determine whether ICAM-1 gene polymorphism influences the risk of developing multiple sclerosis in an Iranian population. We studied 157 patients with definite multiple sclerosis and 156 ethnically matched controls. The patients and the controls were genotyped for ICAM-1 gene polymorphism at codons 241 (exon 4) and 469 (exon 6). G/R241 and K/E 469 allele and genotype distribution did not show any significant difference between patient and control groups. We concluded that role of the ICAM-1 gene polymorphisms in the pathogenesis of multiple sclerosis is still controversial and should be studied further.     

Interleukin-8, intercellular adhesion molecule-1 and tumour necrosis factor-alpha gene polymorphisms and the risk for multiple system atrophy

In a case-control study using a clinically well-defined group of 41 multiple system atrophy (MSA) patients and 93 control subjects, the interleukin (IL)-8 (-251) TT genotype was associated with an approximately fourfold increased risk for MSA and, furthermore, this risk increased elevenfold with the simultaneous presence of the intercellular adhesion molecule-1 (ICAM-1: E469K) KK genotype, suggesting a gene-gene interaction. These data support a role for inflammation-related genes in risk for MSA.     

Multiple sclerosis: The increased frequency of the ICAM-1 exon 6 gene point mutation genetic type K469

Intracellular adhesion molecule-1 (ICAM-1) plays an important role in the cascade of adhesion events in the homing of inflammatory cells to the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). Two single-base ICAM-1 polymorphisms have been described, in exons 4 and 6, changing codons 241 and 469 in the ICAM-1 gene, respectively. Both polymorphisms result in amino acid changes and can potentially lead to different interactions of ICAM-1 with its ligands. To detect ICAM-1 gene polymorphisms in MS, we have developed a highly sensitive and site-specific, two-stage, nested polymerase chain reaction. Genomic DNA was extracted from blood cells of 79 MS patients and 68 control subjects. The results were confirmed by direct dideoxy chain termination sequencing. The frequency of exon 6 allele T was found to be significantly higher in MS patients than in controls (68% vs 49%). Most interesting, the frequency of exon 6 homozygote K469 was significantly higher in MS patients than in controls (53% vs 34%). Higher frequency of the K469 genotype was found to be independent of possible linkage with the previously described MS susceptibility factor, the HLA class II DR2 allele. In the present study, we have shown for the first time the ICAM-1 gene polymorphisms in MS. The results indicate increased frequency of ICAM-1 exon 6 allele T in MS patients, which may contribute to the MS genetics background.     

The ICAM-1 E469K gene polymorphism is a risk factor for spontaneous cervical artery dissection

In a primary study on proinflammatory genetic profiles in stroke, the authors found the E469K polymorphism of the intercellular adhesion molecule 1 (ICAM-1) highly represented in the subgroup with spontaneous cervical artery dissection (sCAD). They further investigated the same genetic variant in a second group of 65 patients with sCAD. An association between sCAD and EE genotype was confirmed (odds ratio 3.16; p < 0.01), indicating that a proinflammatory predisposition is a risk factor for sCAD.     

ABCA1基因R219K多态性与宁夏回、汉族脑梗死患者及血脂的关系

目的探讨宁夏回、汉族脑梗死患者与脂质代谢相关基因三磷酸腺苷结合盒转运子(ABCA1)的R219K多态性及血脂的关系。方法入选我院神经内科脑梗死住院患者266例,其中汉族患者185例(汉族脑梗死组)和回族患者81例(回族脑梗死组)。入院后检测血脂等生化指标,用PCR-RFLP方法测定R219K多态性,统计学方法分析酶切结果及其与血脂的关系。结果回、汉族脑梗死组ABCA1基因R219K基因型(RR、RK、KK)及等位基因频率(R、K)分别为28.4%、60.5%、11.1%,58.6%、41.4%;28.1%、46.5%、25.4%,51.4%、48.6%;汉族脑梗死组与回族脑梗死组等位基因频率分布无显著统计学差异(χ2=1.008,P=0.315),两组间基因型频率差异有统计学意义(χ2=7.647,P=0.022),与RK型比较,回族脑梗死组KK基因型较汉族脑梗死组低(χ2=7.657,P=0.006),将两组进行性别、年龄、高血压、糖尿病等因素亚组分析后,仅回族男性、高血压患者KK基因型较汉族脑梗死组低(χ2=6.725~7.127,P=0.008~0.010);各基因型间血脂水平无统计学差异(P>0.05...     

可诱导协同刺激分子、CD28、CD24基因多态性与多发性硬化的相关性

目的探讨可诱导协同刺激分子（ICOS）、CD28、CD24基因多态性与多发性硬化（multiple sclerosis，MS）遗传易患性的相关性。方法以来自中国汉族人群的83例确诊MS患者和110例非自身免疫性疾病的患者及健康志愿者为研究对象，利用聚合酶链．限制性长度多态性分析（PCR-RFLP）技术检测3个基因扩增产物酶切多态性。结果ICOS-2394位点TT基因型频率MS组明显高于对照组（分别为33．7％和10．9％，P〈0．01），携带T等位基因可增加MS患病危险性（OR=3．482，P〈0．01）；ICOS-2119位点携带C-等位基因MS组明显低于对照组（分别为4．8％和15．5％，P〈0．05）。CD28-372位点基因型等位基因频率分布MS组与对照组差异无统计学意义。CD24 E2＋226位点T等位基因频率MS组较对照组增多（分别为44．6％和33．2％，P〈0．05）。单倍体型关联分析显示CD24 E2＋226T等位基因分别与ICOS-2394T及ICOS-2119C联合可明显增加MS患病危险性，CD28基因多态与ICOS基因多态构成的单体型在MS和对照组中差异无统计学意义。结论中国汉族人群ICOS-2394C／T、ICOS-2119C／T及CD24E2＋226C／T多态性与Ms发病相关，两基因可能均是MS的易患基因或与易患基因相连锁。CD28-372位点多态性与MS患病无直接相关。     

Case-control study of presenilin-1 intronic polymorphism in sporadic early and late onset Alzheimer's disease

OBJECTIVE: Presenilin-1 is a major causative gene for early onset familial Alzheimer's disease, and the apolipoprotein E epsilon4 allele is a major genetic risk factor known to influence late onset and sporadic early onset Alzheimer's disease. The presenilin-1 1/1 genotype has recently been reported to be associated with sporadic Alzheimer's disease. The purpose of this study is to determine whether Alzheimer's disease is associated with presenilin-1 gene polymorphism and the apolipoprotein E genotype in an extended case-control study. METHODS: An examination was conducted on 217 patients with Alzheimer's disease, along with an equal number of age and sex matched controls derived from the same community in a Japanese population, by using a chi2 test for homogeneity and a logistic regression analysis. A meta-analysis of data from the literature on allele frequencies in Alzheimer's disease and control populations was used for comparison with the Japanese allele frequencies obtained in this study. RESULTS: The presenilin-1 allele-1 frequencies were similar in patients with early onset Alzheimer's disease (0.61) and younger controls (0.61), and in those with late onset Alzheimer's disease (0.63) and elderly controls (0. 63). We found no evidence for a possible association between the presenilin-1 polymorphism and the apolipoprotein E epsilon4 allele. However, the meta-analysis showed that the association between the presenilin-1 1/1 genotype and Alzheimer's disease was significant (Peto odds ratio=1.16, 95% confidence interval=1.04-1.31). CONCLUSIONS: These results suggest a subtle but positive association of presenilin-1 gene polymorphism with Alzheimer's disease, although Japanese data in this study which failed to support such a relation would indicate an ethnic variation.