血脂与脑卒中

1脑卒中的现状与危险因素 急性脑血管破裂(脑出血)和阻塞(脑梗死或脑栓塞)引起的疾病统称为脑卒中,是一类危害人们健康的常见病、多发病,其发病率、患病率、致残率、致死率均相当高.在我国,脑卒中是仅次于癌症的第二位致死疾病,每年新发患者＞150万例,现有幸存者＞600万例,其中75%丧失劳动力,40%中度致残,是老年人致残和认知障碍的主要原因.     

缺血性脑卒中患者G蛋白β3亚单位基因C825T多态性及相关危险因素的研究

目的　观察缺血性脑卒中患者G蛋白 β 3亚单位基因 (GNB3)C82 5T多态性和相关危险因素 ,探讨遗传和环境相互作用在缺血性脑卒中发病机制中的作用。方法　急性缺血性脑卒中患者 72例 ,并按性别、年龄配对设对照组。用聚合酶链反应 (PCR)方法扩增目的基因 ,用限制性内切酶 (BseDI)酶切PCR产物用于基因分型 ,同时观察血压、体重指数、饮酒、膳食、性格等。结果　脑卒中组GNB3C82 5T基因型分布 (基因型频率CC =0 .32 ,CT =0 .5 8,TT=0 .10 )与对照组比较 ,差异有显著性意义 (基因型频率CC =0 .6 5 ,CT =0 .32 ,TT =0 .0 3;χ2 =14 .6 ,P <0 .0 1) ,但在脑卒中患者中有或无原发性高血压亚组之间基因型分布无差异。logistic回归分析显示 ,与脑卒中发病有关联的是收缩压 (SBP)、GNB382 5T等位基因、饮酒和空腹血糖 (FPG)升高。结论　SBP、FPG增高、饮酒和GNB3C82 5T多态性的T等位基因可能是缺血性脑卒中发病的危险因素 ,GNB382 5T等位基因对脑卒中的影响不依赖于血压、饮酒等其他危险因素 ,可能是缺血性脑卒中的独立危险因子。     

血管紧张素转换酶基因多态性与老年脑卒中的相关性

目的探讨血管紧张素转换酶(ACE)基因多态性与老年脑卒中的相关性。方法选择186例脑卒中患者(脑卒中组)分为脑血栓组(126例)和脑出血组(60例),另选75例同期住院的非脑卒中患者作为对照组。采用PCR-RFLP技术,检测ACE第16内含子中长度为287bp碱基片段的插入/缺失情况,并分别测定其基因型频率和等位基因频率。结果脑卒中组D等位基因频率为41.9%,对照组为31.3%,两组比较差异有显著性意义(P<0.05);脑卒中组DD型基因频率为21.5%,对照组为9.3%,两组比较差异有显著性意义(P<0.05);脑血栓组和脑出血组D等位基因和DD型基因与对照组比较差异有显著性意义(P<0.05)。结论ACE基因多态性与老年人脑卒中相关,其DD型基因和D等位基因是老年脑卒中的危险因素。     

C反应蛋白基因-717A/G多态性与老年缺血性脑卒中的相关分析

目的探讨C反应蛋白(CRP)基因-717A/G多态性与老年缺血性脑卒中的关系。方法选择年龄≥60岁的缺血性脑卒中患者196例为脑卒中组,同期健康体检者197例为对照组,PCR-RFLP方法检测CRP基因型,并测血清高敏CRP(hs-CRP),logistic回归分析CRP与缺血性脑卒中的关系。结果脑卒中组hs-CRP显著高于对照组(p<0.01),两组CRP基因-717A/G多态性分布无统计学差异(P>0.05)。脑卒中组AA基因型患者hs-CRP浓度显著高于AG+GG基因型[2.30(0.95～3.45)mg/L vs 1.05(0.61～2.12)mg/L,P<0.01],但时照组不同基因型hs-CRP浓度无统计学差异。hs-CRP是老年缺血性脑卒中发生的独立危险因素。结论血清hs-CRP浓度升高与老年脑卒中相关。CRP基因-717A/G多态性与老年缺血性脑卒中无相关性,但与血清hs-CRP浓度有关。     

缺血性脑卒中病情进展的相关因素分析

回顾性分析入院时神经功能评分25分以下的612例缺血性脑卒中患者住院治疗过程中的病情演变情况,入院后每2d进行1次神经功能评分．累计增加10分以上的认定为病情进展。结果病情进展248例（40．52％）．过度应用脱水剂、超早期应用血管扩张剂、急性期应用降压药致使收缩压低于110mmHg及细胞代谢活化剂均可加重病情,四种危险因素同时存在影响尤为突出。缺血性脑卒中的治疗要求规范化,更要个体化,掌握好各种治疗手段的适应证及时机。     

辛伐他汀对血脂异常人群缺血性脑卒中的预防

目的研究辛伐他汀对血脂异常人群缺血性脑卒中的预防作用。方法将2853例血脂异常人群分为预防组(693例)和对照组(2160例),预防组给予辛伐他汀20mg/d,睡前口服。分析2组血脂变化、心脑血管事件、脑卒中等差异。结果预防组受试者糖尿病患病率比对照组高,预防组随访率98．7%,对照组随访率96．2%。预防组低密度脂蛋白胆固醇较对照组低[(2．54±1．01)mmol/L vs(4．12±1．29)mmol/L,P＜0．05],5年生存率高(94．13% vs 83．47%,P＜0．01),缺血性脑卒中和心脑血管事件发生率低。2组死亡的主要原因是:心脑血管疾病、肿瘤和感染。吸烟、高血压、肥胖和糖尿病是脑卒中和心脑血管事件的高危因素。结论辛伐他汀能有效降低血脂异常人群的心脑血管事件。     

CD14启动子-260位点基因多态性对糖尿病肾病的影响

目的探讨CD14启动子-260位点基因多态性对糖尿病肾病（DN）的影响。方法应用PCR直接测序法对437例2型糖尿病（T2DM）患者（T2DM组）及145例正常者（对照组）的CD14启动子C-260T基因多态性进行分析。结果两组CD14启动子-260位点基因型分布及等位基因频率均无统计学差异（P〉0．05）;非DN与DN患者比较,其CD14启动子-260位点CC基因与CT＋TT基因有统计学差异（P〈0．05）。结论CD14启动子-260C／T基因多态性与糖尿病发病无相关性,但其CC基因是T2DM患者进展为DN的遗传学风险因素。     

脑血管反应性降低与缺血性脑卒中的关系

缺血性脑卒中具有高病发率、高致残率、高病死率、高复发率及高医疗费用的特点，但到目前为止，对其真正有效的治疗手段仍很有限，因此寻找缺血性脑卒中的危险因素并及早进行预测、预防就显得格外重要。除了已知的众多危险因素如高血压、糖尿病、血脂异常、冠心病、吸烟、脑卒中家族史及老龄等之外，还有一些危险因素尚待发现。随着研究的不断深入，脑血管反应性降低在缺血性脑卒中发病、发展中的作用逐渐被证实，但尚未引起大家的足够重视，国内的相关研究更为少见。     

缺血性脑卒中相关基因研究进展

脑卒中是一种严重威胁人类健康的疾病,我国脑卒中每年新发病例约150万,而缺血性脑卒中占80%.随着分子生物学和神经科学研究的进展,人们认识到缺血性脑卒中的发病、病理生理过程均与一些基因的表达和调控有着密切的关系.因此,从分子和基因水平对缺血性脑卒中进行研究,探讨通过基因的调控来预防和治疗这类疾病已经成为缺血性脑卒中研究的热点之一.     

纤维蛋白原基因G(-455)A多态性与缺血性脑卒中的关系

目的　探讨缺血性脑卒中与纤维蛋白原基因G( 45 5 )A多态性的关系。方法　利用PCR技术和分子杂交技术对北京地区 2 94例缺血性脑卒中患者进行纤维蛋白原基因G( 45 5 )A多态性位点的检测和分析 ,并与 2 79例北京地区的非脑卒中患者进行比较。结果　缺血性脑卒中患者纤维蛋白原基因G( 45 5 )A多态性的基因型频率和等位基因频率与对照组相比无明显差异。结论　纤维蛋白原基因G( 45 5 )A多态性可能不是缺血性脑卒中发病的遗传学危险因素。     

CD14的基因型及血清水平与急性心肌梗死的关系

目的 研究CD14基因启动子-159C/T、-260C/T多态性各等位基因及基因型在急性心肌梗死(AMI)患者中的分布频率,初步分析其基因型及血清水平与AMI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120例AMI患者及130例正常对照组CD14的基因多态性,同时采用酶联免疫吸附试验(ELISA)检测血清CD14水平.结果 AMI组血清CD14水平显著高于对照组(P<0.01),CD14基因-159C/T多态性在AMI组和正常人群中的分布差异无显著性(P>0.05),而CD14基因-260C/T多态性在两组人群中的分布差异存在显著性(P<0.05),等位基因频率的相对风险分析发现,T等位基因携带者患AMI的风险是C等位基因的1.654倍(OR=1.654,95%CI:1.161～2.356),携带T等位基因的AMI患者血清CD14水平显著高于不携带者(P<0.05).结论 CD14基因启动子-260C/T多态性与AMI的发病具有相关性,其中T等位基因可能是AMI发病的遗传易感基因;携带T等位基因的个体可能通过促进CD14的高度表达进而增加了AMI的发病风险.     

Gene by environment interaction: the -159C/T polymorphism in the promoter region of the CD14 gene modifies the effect of alcohol consumption on serum IgE levels

BACKGROUND: Serum IgE is increased in heavy drinkers. Endotoxin mediates most of the immunological alterations associated with heavy drinking. The -159C/T polymorphism in the promoter region of the gene encoding CD14 (an endotoxin receptor) is associated with serum IgE levels in different populations. AIM: To investigate the possible interaction between alcohol intake and the -159C/T polymorphism in the promoter region of the CD14 gene for serum IgE levels. METHODS: A total of 415 individuals (51.6% males, median age 50 years, range 18-92 years) were studied. A total of 140 individuals were alcohol abstainers, 112 were moderate drinkers (1-280 g/week), and 163 were heavy drinkers (>280 g/week). Main determinations included the CD14/-159C/T genotype, a panel of skin prick tests, total serum IgE, and specific serum IgE against common aeroallergens (Phadiatop test). RESULTS: Heavy drinking was associated with increased total serum IgE values and with positive specific serum IgE to common aeroallergens, but the association was stronger in carriers of the CD14/-159C allele (either CC homozygotes or CT heterozygotes) than in CD14/-159TT homozygotes. Both additive and multiplicative interactions between heavy drinking and the CD14/-159C allele for total and specific serum IgE values was still present after adjusting for potential confounders. Neither alcohol consumption nor the CD14/-159 genotype was associated with skin prick test positivity. CONCLUSIONS: The CD14/-159C/T polymorphism modifies the effect of alcohol consumption on serum IgE levels.     

Common promoter polymorphism in monocyte differentiation antigen CD14 is associated with serum triglyceride levels and body mass index in non-diabetic individuals.

AIMS: Growing evidence supports the hypothesis that chronic low-grade inflammation related to innate immunity may play an important role in the pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation antigen CD14 gene (CD14) acts as the receptor for lipopolysaccharide (LPS) and augments monocyte/macrophage inflammatory responses. METHODS: We have sequenced the gene, including all exons, exon/intron boundaries, and the -1.5 kb of the 5' flanking region. Two common loci (minor allele frequency > 0.05) were genotyped in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study. RESULTS: Eight polymorphisms, including four non-synonymous forms, were identified in CD14. No polymorphisms were found in association with T2DM. However, one common promoter SNP (-260T>C) was significantly associated with both the serum triglyceride level (TG) and body mass index (BMI) in non-diabetic control subjects. Individuals who carried the minor allele (C) had higher TG levels (1.65 +/- 0.81 vs. 1.46 +/- 0.80 mmol/l; P = 0.0007) and BMI (23.96 +/- 3.00 vs. 23.28 +/- 3.22 kg/m(2); P = 0.04) as compared with subjects carrying T/T genotypes. CONCLUSION: Our data suggest that lipid metabolism and obesity, important pathophysiological elements of T2DM and the metabolic syndrome, are regulated by complex mechanisms that include the CD14 gene polymorphism-mediated genetic propensity to non-specific inflammatory responses.     

CD14 promoter polymorphism in Chinese alcoholic patients with cirrhosis of liver and acute pancreatitis

AIM: To investigate the relationship between genetic polymorphism of the CD14 promoter and the occurrence of alcoholic cirrhosis and alcoholic pancreatitis, and to challenge the conclusion made earlier that the patients with acute alcoholic pancreatitis and patients with alcoholic cirrhosis of liver are two different subpopulations. METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the polymorphism of CD14 gene and aldehyde dehydrogenase gene 2 (ALDH 2) in 335 alcoholic patients with different organ complications i.e., cirrhosis of liver (n = 100), acute pancreatitis (n = 100), esophageal cancer (n = 82) and avascular necrosis of hip joint (AVN) (n = 53) and 194 non-alcoholic controls in a Chinese group. RESULTS: The results showed that the carriage of T allele was not different among alcoholic patients with cirrhosis of liver, alcoholic patients with other complication and non-alcoholic controls. On the other hand, the carriage of the C allele was significantly more prevalent for alcoholic pancreatitis than for esophageal cancer (0.79 vs 0.60, P<0.001), alcoholic AVN (0.79 vs 0.65, P<0.025) and nonalcoholic controls (0.79 vs 0.68,P<0.025). Furthermore, when only subjects with ALDH2 1-1 genotype were examined, the C allele frequency was significantly more prevalent for alcoholic pancreatitis than for alcoholic liver cirrhosis (0.82 vs 0.69,P<0.025), esophageal cancer (0.82 vs 0.61,P><0.01), alcoholic AVN (0.82 vs 0.64, P<0.01) and non-alcoholic controls (0.82 vs 0.69, P<0.05). CONCLUSION: The C allele may be associated with some mechanism, which is important in the pathogenesis of alcoholic pancreatitis, and that alcoholic patients with acute pancreatitis and cirrhosis of liver are probably two different subpopulations.     

糖尿病肾病患者血清可溶性CD14水平与血糖、血脂的关系

目的探讨糖尿病肾病（DN）患者血清可溶性CD14（sCD14）水平与血糖、血脂的关系。方法将2型糖尿病（T2DM组）患者分为DN组、非DN组,采用ELISA法检测其与健康者（对照组）的血清sCD14,并分析血清sCD14水平与空腹血糖（FPG）、糖化血红蛋白（HbA1c）、肌酐（sCr）、TC、TG、HDL、LDL的关系。结果T2DM组血清sCD14、FPG、HbA1c明显高于对照组（P均〈0．01）,但两组sCD14与FPG均无相关性（P〉0．05）。DN组血清sCD14水平与HbA1c、LDL呈显著正相关（β=2．89、5．26,P均〈0．05）,与sCr呈显著负相关（β=-0．29,P〈0．05）;非DN组与其均无相关性（P均〉0．05）。结论血清sCD14水平与DN之间存在某些相关性,HbA1c、sCr和LDL是DN的危险因素。     

脂多糖结合蛋白与CD14基因多态性分布及其意义初步探讨

目的通过探讨脂多糖结合蛋白(LBP)Leu436→Phe基因多态性对CD14合成与释放的影响以及CD14 C-159T对LBP蛋白浓度的调节效应,阐明这两种基因多态性的可能作用机制。方法研究对象为118例健康献血员及26例烧伤面积>30%的患者,采用限制性片段长度多态性分析LBPLeu436→Phe及CD14 C-159T基因多态性,同时检测CD14 mRNA表达、可溶性CD14(sCD14)及LBP浓度。结果体外全血培养实验中,脂多糖刺激与否,LBPLeu436→Phe对CD14 mRNA表达、sCD14水平均无明显影响(P>0.05),CD14-159位点基因型也与LBP浓度无关(P>0.05)。而对烧伤面积>30%的患者研究显示,CD14-159位点TT基因型患者LBP浓度于伤后第3、21天明显高于CC基因型(P<0.05)。结论CD14 C-159T基因多态性可能通过间接调节机制影响LBP产生,并与严重烧伤患者预后不良有关。     

Association between CD14 gene promoter polymorphisms with serum total-IgE and eosinophil levels in atopic and non-atopic asthma patients in a Chinese Han population

Objective: The aim of this study was to investigate the association between CD14 gene promoter SNPs with serum total-IgE and eosinophil levels in atopic asthma and non-atopic asthma in Chinese Han. Methods: A total of 152 patients with asthma were divided into atopic asthma (n?=?100) and non-atopic asthma (n?=?52) groups for this study. Six CD14 gene SNPs were analyzed using PCR and gene sequencing. Serum total-IgE and eosinophil levels were measured. The association between genotype frequencies of the CD14 gene loci with total-IgE and eosinophil levels in atopic asthma and non-atopic asthma was evaluated by the ANOVA test method. Hundred and sixteen healthy subjects constitute the control group. Results: We found that serum total-IgE and eosinophil levels were significantly higher in individuals with atopic asthma when compared to individuals with non-atopic asthma (p?<?0.01). For non-atopic asthma, the total-IgE levels of the heterozygous genotypes were significantly higher than the corresponding levels for the homozygous genotypes in CD14-260C?>?T, CD-651C?>?T, CD-911A?>?C and CD-1247A?>?G (p?<?0.01). In atopic asthma, there was no statistical significance for either serum total-IgE or eosinophil levels among the genotypes of the CD14 gene SNPs. In addition, allele A frequency of CD14-1247A?>?G was significantly different between the atopic asthma and non-atopic asthma groups (p?=?0.025). Conclusions: There was a statistical association between the serum total-IgE level and the CD14 gene promoter SNPs in the non-atopic asthma group. The eosinophil level was not found to be statistically associated with the CD14 gene promoter SNPs in either the atopic asthma or non-atopic asthma groups.     

Influence of C-159T SNP of the CD14 gene promoter on lung function in smokers

CD14, a co-receptor for endotoxin, plays a significant role in regulating the inflammatory response to this agent. The C-159T single nucleotide polymorphism (SNP) in the CD14 gene promoter is an important regulator of CD14 expression, with TT homozygotes having increased expression of CD14. This SNP has been linked to pathogenesis of asthma and with cardiovascular diseases in smokers. We hypothesize that CD14 also plays a role in the pathophysiology of COPD in smokers who are exposed to endotoxin contained in cigarette smoke as well as endotoxin derived from Gram-negative microbes colonizing their airways. To assess the effect of the C-159T SNP of the CD14 gene promoter on lung function, we recruited 246 smokers 40 years of age or older with a range of 10–156 pack-year smoking exposures. The TT genotype was associated with lower lung function in smokers with a moderate smoking history. However, the CC genotype was associated with decreased lung function in heavy smokers (>56 pack years). The effect of CC genotype on severity of COPD is analogous with the effect of this genotype in risk for asthma. CD14 may be a factor in the pathophysiology of COPD, as it is in asthma and smoking-related cardiovascular diseases.     

CD14启动子-159位点基因多态性与糖尿病肾病的相关性研究

者在10年和20年时,发生DN的百分率分别为13.3%和23.4%;纯合子CC基因型2型糖尿病患者发生DN的风险高于CT+TT基因型患者.结论 CD14启动子C-159T基因多态性与糖尿病的发病无关,但其中的CC纯合子基因是2型糖尿病患者进展为DN的遗传学风险因素.